bims-ribost Biomed News
on Ribostasis and translation stress
Issue of 2026–06–28
eighty-two papers selected by
Cédric Chaveroux, CNRS
  1. The role of RNA modifications in cancer translational control.
  2. Trm7/FTSJ1-Mediated tRNA Anticodon-Loop 2'-O-Methylation: From Structural Mechanisms to Translational Dysfunction and Disease.
  3. Structural insights into the recruitment of viral type 2 IRES to ribosomal preinitiation complex for protein synthesis.
  4. Isoginkgetin increases the expression of metal responsive transcripts but inhibits their translation.
  5. Transcription Start Site Choice Regulates m6A Stoichiometry in Cap-Proximal Regions.
  6. Quantitative profiling of RNA modifications enriched in non-membrane-bound cellular structures using APEX-RNA-MS.
  7. Translational activation: An unforeseen function of RNP biomolecular condensates.
  8. Optimized tRNA structure-seq reveals robust tRNA secondary structures in S. cerevisiae under mild stress conditions.
  9. Cryo-EM structure of the Arabidopsisthaliana ribosome in translating and non-translating states.
  10. Pseudouridine synthase PUS1 and initiation factor mtIF2 are human mitoribosomal small subunit assembly factors.
  11. Suppressed SF3B1 Expression Lowers METTL3 Transcription and m6A RNA Expression.
  12. m6A in RNA: a key regulator of brain development, function and disease.
  13. A ribosomal kinetic checkpoint governs selective mRNA recruitment.
  14. Selenoprotein S plays a role in translation and membrane protein biogenesis.
  15. Enhancing ribosomal translation of backbone-altering nonproteinogenic amino acids via YebC and YeeN.
  16. MDM2 suppresses c-Myc synthesis by binding to the 5' mRNA translation regulatory sequence.
  17. The Late Evolution of the Nascent Peptide Code for Translational Control and Its Relationship to the Standard Genetic Code.
  18. Transfer RNA (tRNA) Genes, Codon Usage and Translational Efficiency in Leishmania infantum.
  19. An isotype-specific phosphorylation of Hsp90 rewires co-chaperone regulations.
  20. Nuclear determinants of mRNA and protein isoforms.
  21. Single-cell heterogeneity in ribosome levels and protein synthesis during nutrient starvation is driven by cAMP signaling.
  22. The p97 adaptor p47/NSFL1C is necessary for stress granule dissolution after heat stress.
  23. RNASET2 degrades mRNAs that protect against lipotoxicity.
  24. Alternate RNA decoding results in stable and abundant proteins in mammals.
  25. m6A-FORM: An m6A-focused Foundation Model for Decoding m6A Regulatory Function.
  26. Target of Rapamycin Coordinates Metabolic Remodeling at the Protein Level in the Red Alga Cyanidioschyzon merolae.
  27. Beyond Hydrogen Sulfide and Cysteine Metabolism: Reframing Cystathionine γ-Lyase as a Potential Translational Regulator of Hypoxia-Inducible Factor-1α in Clear Cell Ovarian Carcinoma.
  28. Epitranscriptomics in Breast Cancer: The Unveiled Role of RNA Modifications.
  29. CCR4-NOT is required for suppressing pervasive transcription and retrotransposable elements.
  30. Dual functions of thermospermine in plant growth and stress responses.
  31. Modulation of Stress and Anabolic Signalling Pathways by Whey Protein Isolate in C2C12 Cells Under Exercise-Mimetic Conditions.
  32. mRNA-Scaffolded Cytoplasmic Compartments.
  33. Reduced Sensitivity to RNA Structural Differences Distinguishes Eukaryotic Pus4 from Bacterial TruB.
  34. m6A RNA Methylation-miRNA Crosstalk in Cardiovascular Remodeling.
  35. Epigenetic regulation of cuproptosis in cancer: mechanisms, microenvironment, and therapeutic implications.
  36. Alternative Splicing in Plant Development and Abiotic Stress Responses: A Multifunctional Regulatory Mechanism.
  37. Translational Regulation of Sf1 Integrates Alternative Splicing and Hematopoietic Stem Cell Fate.
  38. Targeting RNA quality-control defects in tauopathies: Pharmacodynamic biomarkers and therapeutic development.
  39. The Interplay of Splicing and Metabolism in Cancer.
  40. UPF1 at Work: Structural and Mechanistic Insights into a Master Regulator of Nonsense-Mediated mRNA Decay.
  41. RNA-Protein complexes and their role in cell fate.
  42. Antisense RNA controls the degradation of phycobilisomes in heterocyst-forming cyanobacteria by a transcriptional interference mechanism.
  43. Predicted bacterial uRBSs reveal translational coupling and ribosome-mediated RBS occlusion as gene-controlling mechanisms.
  44. Heat stress reveals bidirectional cross talk between the heat shock response and UPRER in C. elegans.
  45. The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.
  46. The oxidative cost of losing low temperature viability protein 1 [Ltv1]: insights into cellular damage and homeostasis.
  47. The diverse effects of stress in cross-feeding systems.
  48. Neuron type-specific translatomes in dorsal hippocampus during early memory consolidation.
  49. Heat Shock Proteins in Medically Relevant Fungal Pathogens: From Molecular Chaperones to Virulence Factors and Therapeutic Targets.
  50. p53 overrides METTL5 loss-induced tumor suppression via mitochondrial respiration.
  51. RNA-Binding Protein Occupancy Composition Predicts Long Noncoding RNA Subcellular Localization.
  52. Conserved HSP60 structure with lineage- and context-specific regulation in cnidarians.
  53. N7-Methylguanosine Modification in Colorectal Cancer: Molecular Insights and Clinical Implications.
  54. The transcriptional and translational outcomes for pseudogenes in bacterial endosymbionts.
  55. Activation of the antibiotic resistance factor WhiB7 can stimulate aggregate biofilm formation in stationary phase Mycobacterium smegmatis by reinitiating translation.
  56. PKCβII Activation Promotes Membrane-Proximal Enrichment of Ribosome-Bound RACK1.
  57. Hidden Messages in Extracellular Vesicles: Cross-Kingdom RNA Communication in Plant and Microbe Interactions.
  58. Engineering bone tissue with mRNA: from molecular design and delivery to clinical applications.
  59. N-terminal modifications as fate switches in neurodegeneration: a mechanistic review.
  60. Relative abundance of genes regulating proliferation and apoptosis of corpus luteum during cold and hot seasons in Egyptian buffaloes.
  61. RNA-Binding Proteins in Ageing and Age-Related Disease.
  62. STMN2 protein depletion via translation deficits and stress granules in amyotrophic lateral sclerosis.
  63. Immunoelectroanalytical multiplexing of RNA methylation signatures to decode oncogenic point mutations in cancer cells.
  64. Enhanced IGFL1 translation in response to IL-1β is controlled by distinct 3'UTR elements.
  65. RNA G-quadruplexes function as a tunable switch of FUS phase separation.
  66. Genes associated with translation and oxidative phosphorylation as components of the translational response in nodulated and water-restricted soybean.
  67. The mRNA covalent modification dihydrouridine regulates transcript turnover and photosynthetic capacity during plant abiotic stress.
  68. β-TrCP targets nucleolin and modulates phase separation to restrict ribosome biogenesis in myocardial infarction hearts.
  69. The Research Progress in Targeted Therapy for Hypertension via Heat Shock Proteins.
  70. Establishment and validation of the NEX-RiboTag system for profiling the excitatory neuronal translatome in the postnatal mouse forebrain.
  71. RNA modifications shape innate immunity and cellular adaptation during bacterial respiratory infection.
  72. From activation to desensitization: How ABA balances plant growth and abiotic stress response?
  73. Temporal proteomic analysis reveals a three-phase adaptation strategy in Phytophthora cinnamomi during salinity stress.
  74. Size-Dependent Layered Double Hydroxide Nanoparticles Promote Osteogenesis and Bone Regeneration via METTL3-Dependent N6-Methyladenosine Modification of Runx2 mRNA.
  75. Synthetic Mirror Bacteria as a Frontier for Chiral Synthetic Biology and Biocontainment.
  76. Molecular Equilibrist: The Small Heat Shock Protein IbpA from Mycoplasma.
  77. RNA variation as the driver of genomic efficiency and phenotypic complexity.
  78. Robust and sensitive ELISA detection of total and activated PRKN.
  79. HENMT1: an RNA methyltransferase in biology and disease.
  80. Carboplatin Elicits ROS Responses and Potentially Regulates Translation Program in Cancer Systems.
  81. RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis.
  82. Genome-Wide Characterization and Expression Profiling of Putative m6A Methylation Regulatory Proteins (Writers and Erasers) in Ginkgo biloba.
  1. RNA Biol. 2026 Jun 24.
    The role of RNA modifications in cancer translational control.
    Merin Joy, Alice Cleynen, Nikolay E Shirokikh.
      RNA modifications have emerged as central regulators of cancer translational control. Unlike transcriptional reprogramming, which unfolds over hours, modification-dependent translational rewiring enables rapid proteomic adaptation to the nutrient-deprived, hypoxic, and immunologically hostile tumour microenvironment. Yet most existing reviews organize epitranscriptomic mechanisms by modification type or cancer hallmark, obscuring the mechanistic logic by which chemical marks collectively reshape the translational apparatus. This review adopts a translation-centric framework, examining how the most abundant modifications on mRNAs, tRNAs, and rRNAs regulate each stage of protein synthesis in malignant cells. We survey the epitranscriptomic toolkit, including modification chemistries, enzymatic writers, readers, and erasers, and detection technologies including nanopore direct RNA sequencing. We then trace how modifications control initiation (m6A-driven mRNA circularization, cap-independent translation via eIF3 and eIF4G2, rRNA 2'-O-methylation-directed cap-to-IRES switching), elongation (m6A-induced ribosome stalling coupled to mRNA decay, tRNA mcm5s2U-mediated codon-biased translation, YTHDF1-dependent elongation factor recruitment), and termination (pseudouridine-mediated stop codon readthrough, NMD evasion). Crucially, we show that mRNA, tRNA, and rRNA modifications do not act in isolation but form integrated networks. For example, mRNA m6A and tRNA mcm5s2U operate on opposing arms of the same regulatory axis, with direct implications for therapeutic design. We assess the expanding drug pipeline, from the METTL3 inhibitor STC-15 now in Phase 1b/2 trials and METTL3-targeting PROTACs to FTO and ADAR1 inhibitors, and argue that biology-informed combination strategies targeting multiple modification axes will be essential for durable clinical responses.
    Keywords:  RNA modifications; cancer translation; epitranscriptomics; m6A; ribosome heterogeneity; translational control
    DOI:  https://doi.org/10.1080/15476286.2026.2694854
  2. Genes (Basel). 2026 Jun 15. pii: 697. [Epub ahead of print]17(6):
    Trm7/FTSJ1-Mediated tRNA Anticodon-Loop 2'-O-Methylation: From Structural Mechanisms to Translational Dysfunction and Disease.
    Huan Sheng, Jun Yao.
      Transfer RNAs (tRNAs) are chemically matured decoding molecules that are central to protein synthesis. Their post-transcriptional modifications, especially those in the anticodon stem-loop (ASL), shape local RNA structure, codon recognition and translational fidelity at the tRNA-mRNA decoding interface. 2'-O-methylation (Nm) is a conserved ribose modification installed at selected ASL positions, particularly positions 32 and 34, by the modular Trm7/FTSJ1 methyltransferase system. Rather than directly changing base-pairing identity, these marks help prepare the decoder for efficient translation and function within an interconnected 32-34-37 modification network, best illustrated by tRNAPhe. Loss of Trm7/FTSJ1-mediated Nm may impair selected codon-tRNA decoding pairs; in yeast, Trm7 deficiency is additionally associated with GAAC activation and phenotypes consistent with reduced functional tRNAPhe availability. In humans, mutations in FTSJ1 are associated with nonsyndromic X-linked intellectual disability (NSXLID), suggesting that disruption of tRNA chemical maturation can affect neuronal translation programs. In this review, we integrate anticodon-loop modifications at positions 32, 34, and 37 into a decoder-centered framework and compare the conserved enzymatic logic of yeast Trm7 and human FTSJ1 with their divergent substrate repertoires. By synthesizing structural, biochemical, genetic, and translational evidence, we distinguish established mechanisms from working models and unresolved questions concerning tRNA modification hierarchies and neuronal vulnerability.
    Keywords:  2′-O-methylation; Trm7/FTSJ1; anticodon stem-loop; codon-biased translation; neurodevelopmental disease; tRNA modification; tRNAPhe
    DOI:  https://doi.org/10.3390/genes17060697
  3. Elife. 2026 Jun 25. pii: RP107788. [Epub ahead of print]14
    Structural insights into the recruitment of viral type 2 IRES to ribosomal preinitiation complex for protein synthesis.
    Deepakash Das, Tanweer Hussain.
      Picornaviruses employ internal ribosome entry sites (IRESs) in their genomic RNA to hijack the host's translational machinery. The picornavirus, encephalomyocarditis virus, employs a type 2 IRES present in its 5' untranslated region (5'UTR) and requires 43S ribosomal preinitiation complex (PIC), the central domain of eukaryotic initiation factor (eIF) 4G, eIF4A, and an essential ITAF (IRES trans-acting factor)-polypyrimidine tract binding protein 1 (PTB1) to form 48S PIC. In this study, we have used cryo-electron microscopy (cryo-EM) to determine the structure of encephalomyocarditis virus (EMCV) IRES-bound mammalian 48S PIC in a scanning-arrested closed state at the start codon. The EMCV IRES domains contact initiator tRNA (tRNAi) and 40S head at the inter-subunit interface, which reveals an altogether unique mechanism used by viruses to capture host translational machinery for its protein synthesis. The tRNAi is held away from the 40S body in contrast to canonical cap-dependent translation while the domain I apical region of EMCV IRES mimics 28S rRNA of 60S to interact with 40S ribosomal head proteins uS13 and uS19. The structural analysis accounts for numerous previously reported biochemical studies on type 2 IRES and shows how type 2 IRES interacts with 43S PIC to form 48S PIC. This study provides mechanistic insights for understanding EMCV IRES-mediated translation initiation, which could be extrapolated to other IRESs sharing similar motifs and factor requirements, including type 1 viral IRESs.
    Keywords:  48S preinitiation complex; biochemistry; chemical biology; host ribosome; internal ribosome entry sites; molecular biophysics; structural biology
    DOI:  https://doi.org/10.7554/eLife.107788
  4. PLoS One. 2026 ;21(6): e0352014
    Isoginkgetin increases the expression of metal responsive transcripts but inhibits their translation.
    Claire Peneycad, Erin van Zyl, Abhinav Mohur, Bruce C McKay.
      Isoginkgetin (IGG) is a natural bioflavonoid isolated initially from leaf extracts of Gingko biloba trees used in traditional Chinese medicine. We previously reported that IGG strongly inhibits nascent protein synthesis by activating the shared ATF4-dependent branches of the integrated stress response (ISR) and the unfolded protein response (UPR). Here we sought to characterize an ATF4-independent response to IGG that leads to increased expression of mRNAs encoding metallothionines (MTs) and a zinc transporter (ZnT1). We confirm that IGG induces MT1F, MT1X, MT2A and ZnT1 mRNAs in several independent cell lines. We also find that siRNA-mediated knockdown of the metal regulatory transcription factor 1 (MTF-1) reduced basal and IGG-induced levels of these mRNAs. Curiously, we did not detect increased expression of these proteins following exposure to IGG. To study the dissociation between transcription and translation of metal responsive mRNAs, we created a stable cell line expressing a luciferase reporter gene under control of five metal response elements. Our positive control (ZnSO4) increased luciferase activity as expected but IGG reduced luciferase activity. Importantly, IGG, and other inhibitors of translation, prevented the increase in luciferase activity when combined with ZnSO4 without affecting the ZnSO4-induced increase in luciferase mRNA levels. We propose that IGG activates ATF4- and MTF-1-dependent transcriptional responses but that IGG simultaneously impairs nascent protein synthesis and masks the metal response at the protein level.
    DOI:  https://doi.org/10.1371/journal.pone.0352014
  5. Genes (Basel). 2026 May 31. pii: 653. [Epub ahead of print]17(6):
    Transcription Start Site Choice Regulates m6A Stoichiometry in Cap-Proximal Regions.
    Jianheng Fox Liu, Samie R Jaffrey.
      Background/Objectives:N6-methyladenosine (m6A) is the most prevalent and functionally significant internal modification within eukaryotic mRNA. While m6A is known to be regulated at internal sites by factors such as splice junctions, the mechanisms governing deposition within the cap-proximal region remain poorly understood. This study aims to determine the patterns of m6A stoichiometry in cap-proximal regions and to investigate whether the choice of the specific transcription start site (TSS) can affect m6A stoichiometry. Methods: We re-analyzed our published single-nucleotide-resolution CROWN-seq data to quantify m6A stoichiometry across transcript isoforms with different TSSs, and assessed the relationship between specific TSSs and specific m6A sites ("TSS-m6A-site pairs"). Results: We established the first single-nucleotide-resolution dataset of m6A stoichiometry across the transcriptome in cap proximal regions, including stoichiometry of m6A across 5' isoforms for each gene. We found that m6A deposition is markedly inhibited within a narrow cap-proximal region in a distance-sensitive manner. m6A sites located close to both 5' and 3' exon ends exhibit low methylation due to the overlap between the cap-proximal and 3' exon-end exclusion zones. Conclusions: We find that the first exon contains a narrow m6A exclusion zone at its 5' end. As a result, cap-proximal m6A sites can have different stoichiometries depending on the TSS choice. As the m6A site is positioned farther from the TSS, m6A stoichiometry increases. These results reveal that TSS switching is a regulatory mechanism for m6A stoichiometry in cap-proximal regions and provide a mechanism for fine-tuning gene expression and mRNA fate through isoform-specific m6A modification stoichiometry.
    Keywords:  5′ UTR; CROWN-seq; GLORI; RNA modification; cap-proximal region; m6A; m6Am; transcription start site
    DOI:  https://doi.org/10.3390/genes17060653
  6. Cell Chem Biol. 2026 Jun 22. pii: S2451-9456(26)00191-1. [Epub ahead of print]
    Quantitative profiling of RNA modifications enriched in non-membrane-bound cellular structures using APEX-RNA-MS.
    Kyung W Seo, Dhruv Y Dhingani, Ralph E Kleiner.
      The dynamic behavior of RNAs underlies fundamental biological processes. RNA function is controlled by post-transcriptional modifications that are spatiotemporally regulated, but characterizing the distribution of modified RNA transcripts with subcellular resolution is a major challenge. Here, we present APEX-RNA-MS, which combines APEX2 proximity labeling with liquid chromatography-mass spectrometry (LC-MS) quantification of modified ribonucleotides. We use APEX-RNA-MS to characterize RNA modifications proximal to RNA-binding proteins enriched in non-membrane-bound cellular structures. We measure changes in protein-proximal RNA modification levels upon induction of DNA damage foci and stress granules, consistent with previous studies using antibody-based imaging and biochemical fractionation. Further, we show that tRNA-specific modifications are proximal to G3BP1 and use RNA sequencing and RNA fluorescence in situ hybridization (FISH) to demonstrate the accumulation of multiple tRNAs in stress granules. Taken together, our work provides a general approach for characterizing the subcellular distribution of RNA modifications and reveals new insights into the composition and function of cellular condensates.
    Keywords:  APEX; DNA damage; P-bodies; RNA mass spectrometry; RNA modifications; proximity labeling; stress granules
    DOI:  https://doi.org/10.1016/j.chembiol.2026.05.012
  7. Mol Cell. 2026 Jun 23. pii: S1097-2765(26)00375-8. [Epub ahead of print]
    Translational activation: An unforeseen function of RNP biomolecular condensates.
    Ali Haidar, Anne Ramat, Martine Simonelig.
      Biomolecular condensates are emerging structures that organize cell biochemistry. RNA-protein (RNP) condensates have raised huge interest in the field of RNA biology due to their potential to impact gene expression. Although RNP condensate biophysical properties and assembly mechanisms have been extensively studied, leading to major breakthroughs, their contribution to biological processes remains debated. In this perspective, we review the current knowledge on the functions of cytoplasmic RNP condensates in mRNA regulation. Particularly, we highlight recent technological and conceptual advances that revealed the unexpected function of RNP condensates in mRNA translation. We discuss the mechanisms and biophysical bases that reconcile RNP condensate dual function in translational repression and activation. We propose emerging future directions to further address translation at RNP condensates and decode their functional compartmentalization linked to their biophysical properties. We also highlight the importance of this new function of condensates in translation for improved RNA-based therapeutics.
    Keywords:  Suntag; biomolecular condensates; biophysical properties; germ granules; mRNA storage; multiphasic condensates; stress granules; translation; translational repression
    DOI:  https://doi.org/10.1016/j.molcel.2026.06.004
  8. RNA. 2026 Jun 26. pii: rna.081029.126. [Epub ahead of print]
    Optimized tRNA structure-seq reveals robust tRNA secondary structures in S. cerevisiae under mild stress conditions.
    Komei Yanagihara, Futa Konishi, Teppei Matsuda, Akira Hirata, Hiroyuki Hori, Philip C Bevilacqua, Ryota Yamagami.
      RNA structure plays a crucial role in diverse biological processes beyond the translation of genetic information. Therefore, the development of reliable methods for RNA structure prediction is essential for understanding RNA structure-related functions, however accurate and comprehensive RNA structure prediction remains challenging. Here, we focus on secondary structure prediction of transfer RNA (tRNA) using structure probing coupled with next-generation sequencing (tRNA Structure-seq). In silico prediction of Saccharomyces cerevisiae tRNA secondary structures achieves only 56.9% accuracy on average. Incorporation of dimethyl sulfate (DMS) probing data improve prediction accuracy to 87.4%, which is still not sufficient for practical tRNA structure prediction. To overcome this, we optimized the tRNA Structure-seq analysis pipeline by explicitly incorporating natural tRNA modifications detected in tRNA sequencing data and by refining pseudo-free energy parameters specifically optimized for tRNA structure prediction. Using this optimized pipeline, the average prediction accuracy is remarkably improved to 93.3%. Furthermore, analysis of multiple structural conformations predicted from DMS probing data indicates that S. cerevisiae tRNAs predominantly adopt the canonical cloverleaf secondary structure under in vivo conditions. Finally, we examined tRNA structures under mild stress conditions, including heat stress, osmotic stress, and antibiotic stress. These perturbations had minimal effects on in vivo tRNA secondary structure, demonstrating that S. cerevisiae tRNAs maintain structural stability under physiologically relevant stress conditions. In summary, our results establish an optimized tRNA Structure-seq analysis that enables highly accurate tRNA secondary structure prediction and reveals the intrinsic robustness of tRNA structures in living cells.
    Keywords:  mutation profiling; prediction of RNA structure; tRNA; tRNA modification; tRNA structure
    DOI:  https://doi.org/10.1261/rna.081029.126
  9. Structure. 2026 Jun 26. pii: S0969-2126(26)00182-6. [Epub ahead of print]
    Cryo-EM structure of the Arabidopsisthaliana ribosome in translating and non-translating states.
    Sudeep Karki, Xun Lu, Anja O Paatero, Raili Ruonala, Dale Tranter, Sergey Guryanov, Shahid Rehan, Eva Hellmann, Anders Haakonsson, Sarah J Butcher, Juha T Huiskonen, Tommi Kajander, Yrjö Helariutta, Ville O Paavilainen.
      Translational control of mRNA expression underpins much of post-transcriptional gene expression driving developmental processes in eukaryotes. How ribosomal mRNA translation is executed in plants may be especially important for adapting to an ever-changing environment. Arabidopsis thaliana is the main genetic model organism in plant science, yet structural insights into developmental processes where ribosomal gene expression plays important roles currently remain lacking. Here, we present cryoelectron microscopy (cryo-EM) structures of the Arabidopsis cytosolic ribosome in both translating and non-translating states, which together provide new structural details into how translation of cytosolic mRNAs is coordinated. Our structures reveal detailed information on the interactions of tRNAs, mRNA, and the nascent polypeptide with subunits of the actively translating 80S ribosome and the role of ribosomal RNA methylation in stabilizing ribosomal subunits. The structures provide a foundation for interpreting the functional effects of many mutations of ribosomal proteins affecting phenotypic effects for plant tissue development.
    Keywords:  Arabidopsis thaliana; Protein synthesis; cryo-EM; plant science; ribosome
    DOI:  https://doi.org/10.1016/j.str.2026.06.001
  10. Nat Commun. 2026 Jun 24. pii: 5564. [Epub ahead of print]17(1):
    Pseudouridine synthase PUS1 and initiation factor mtIF2 are human mitoribosomal small subunit assembly factors.
    Vivek Singh, Dmitrii Shiriaev, Lorina Bilalli, Anas Khawaja, Joanna Rorbach.
      Assembly of the mitochondrial ribosome (mitoribosome) is a crucial step in mitochondrial gene expression. This process facilitates mitochondrial translation, which produces essential subunits of the oxidative phosphorylation machinery-the cell's primary energy-producing machinery. Disruptions in mitoribosome assembly can lead to severe human diseases. Given its fundamental importance, detailed structural analysis of mitoribosome assembly pathways is essential for advancing our understanding of mitochondrial function in both health and disease. In this study, we characterize twelve distinct assembly states of the mitoribosomal small subunit (mtSSU) isolated from human cells. Our findings reveal the intricate details of the final maturation stages of the mtSSU platform, decoding center, and the 3'-end of 12S rRNA. This process is governed by coordinated actions of assembly factors that ensure precise, stepwise rRNA folding and the integration of mitoribosomal proteins into the developing subunit. Our approach identifies pseudouridine synthase PUS1 and initiation factor mtIF2 as assembly factors, expanding their known roles beyond mt-tRNA maturation and translation, respectively. In addition, the identified assembly intermediates provide insight into the modular nature of mtSSU biogenesis in mitochondria and further link late-stage assembly to the acquisition of translational competence.
    DOI:  https://doi.org/10.1038/s41467-026-74700-x
  11. Int J Mol Sci. 2026 Jun 15. pii: 5396. [Epub ahead of print]27(12):
    Suppressed SF3B1 Expression Lowers METTL3 Transcription and m6A RNA Expression.
    Namjeong Choi, Hina Ashraf, Haihong Shen.
      Splicing factor 3b1 (SF3B1), a component of U2 small nuclear ribonucleoprotein (U2 snRNP), has been known for its essential roles in pre-mRNA splicing and alternative splicing. Here we show that knocking down (KD) of SF3B1 broadly induced a significant reduction in mRNA expression in the genome. One of the genes whose expression is reduced by SF3B1 KD is methyl-transferase-like 3 (METTL3), a writer of N6-methyladenosine (m6A). We demonstrate that expression of both METTL3 mRNA and protein is affected by SF3B1 KD, which further decreases the m6A RNA expression level. m6A-seq indicates that SF3B1 KD affects m6A distribution within multiple genes in the genome. In addition, a high proportion of hypo-methylation events by SF3B1 KD (~70%) are overlapped in METTL3 KD cells, and a conserved m6A motif is observed in the hypo-methylated regions as in SF3B1 KD cells, suggesting the m6A decrease by SF3B1 is a direct effect of the reduced METTL3 expression. Furthermore, RT-qPCR using unlabeled RNA and 5-Bromouridine (BrU)-labeled nascent RNA and actinomycin D treatment demonstrates that transcription of METTL3 is significantly reduced but the mRNA decay rate is not altered, suggesting that METTL3 expression is altered at the transcription level. We further show that SF3B1 interacts with RNA polymerase (Pol) II in the RNA independent manner, further indicating the involvement of SF3B1 in transcription. Lastly, we demonstrate that the transcription inactive H3K27me3 on the METTL3 promoter was significantly increased whereas transcription active H3K4me3 was not changed by SF3B1 KD. Taken together, we conclude that reduced SF3B1 expression suppresses the transcription of METTL3 and inhibits m6A RNA expression.
    Keywords:  METTL3; SF3B1; m6A; transcription
    DOI:  https://doi.org/10.3390/ijms27125396
  12. Nat Rev Neurosci. 2026 Jun 22.
    m6A in RNA: a key regulator of brain development, function and disease.
    Enakshi Sivasudhan, Kate D Meyer.
      Epitranscriptomic regulation of cellular RNAs is a major mechanism of gene expression control in the brain. N6-Methyladenosine (m6A) is installed on thousands of mRNAs and non-coding RNAs, where it functions as a context-dependent regulator of RNA-protein interactions to control the amplitude and kinetics of gene expression. In the nervous system, m6A is critical for neurodevelopment, synaptic plasticity and adaptive responses to physiological stimuli, and its dysregulation has been linked to various brain disorders. In this Review, we present a comprehensive synthesis of how m6A is deposited, interpreted and dynamically regulated, and integrate recent advances to present a unified framework for its function in neural cells. We discuss how m6A coordinates RNA stability, translation, localization and chromatin-associated processes across developmental and adult contexts and how disruption of these pathways contributes to neurological disease. Finally, we explore challenges and future directions for the field.
    DOI:  https://doi.org/10.1038/s41583-026-01056-y
  13. bioRxiv. 2026 Jun 13. pii: 2026.06.12.731988. [Epub ahead of print]
    A ribosomal kinetic checkpoint governs selective mRNA recruitment.
    Masaaki Sokabe, Carlos Alvarado, Christopher P Lapointe, Nancy Villa, Joseph D Puglisi, Christopher S Fraser.
      Translation initiation begins with recruitment of mRNA to the ribosome, yet how mRNA engagement is converted into productive initiation remains unclear. Using real-time fluorescence assays with purified components, we show that mRNA recruitment proceeds through a branched kinetic pathway on the 40S subunit. Following rapid sampling, mRNAs partition into either a productive accommodated state or an arrested state that stabilizes ribosome binding before accommodation. mRNA structure, eIF3, and eIF3j bias recruitment toward arrest, whereas eIF4F promotes accommodation in an ATP-dependent manner coupled to displacement of eIF3j from the mRNA entry channel. Unstructured mRNAs accommodate independently of eIF4E, whereas structured mRNAs require an upstream eIF4E-dependent step, enabling selective recruitment under limiting eIF4E. Arrested complexes can convert directly into the accommodated state without dissociation, revealing a reversible standby intermediate poised for activation. Together, our findings establish mRNA accommodation as a ribosome-intrinsic checkpoint governing initiation and provide a framework for selective translation.
    DOI:  https://doi.org/10.64898/2026.06.12.731988
  14. bioRxiv. 2026 Jun 16. pii: 2026.06.08.725543. [Epub ahead of print]
    Selenoprotein S plays a role in translation and membrane protein biogenesis.
    Farid Ghelichkhani, Mariia A Kapitonova, Atinuke Odunsi, Erfan Rahmani, Omar G Rosas Bringas, Mohammed Hanzala Kaniyar, John LaCava, Sharon Rozovsky.
      Human selenoprotein S (selenos) is part of the integrated cellular stress response and linked to protein quality control and signaling pathways. Consequently, genetic polymorphisms of selenos are associated with increased risk for diabetes, dyslipidemia, and cardiovascular diseases. Determining the specific roles of selenos in these cellular pathways and diseases has been challenging, as selenos associates with a wide range of protein complexes. Thus, to map the cellular functions of selenos and uncover their interconnections, we used affinity purification and in vivo crosslinking to stabilize transient protein interactions, followed by proteomics to record the resulting selenos interactome. Through mapping of selenos protein partners, we found evidence that selenos associates with complexes responsible for the insertion of membrane proteins into the ER bilayer and their connected quality control components. Furthermore, selenos is also part of metabolic, trafficking, and mitochondrial pathways. Notably, proteins involved in translation preferentially associate with selenos when its C-terminal intrinsically disordered segment containing the redox-active motif is accessible. Together, these results identify the C-terminal redox loop of selenos as a central interaction hub connecting translation with ER membrane protein biogenesis and quality control.
    DOI:  https://doi.org/10.64898/2026.06.08.725543
  15. Nucleic Acids Res. 2026 Jun 22. pii: gkag617. [Epub ahead of print]54(12):
    Enhancing ribosomal translation of backbone-altering nonproteinogenic amino acids via YebC and YeeN.
    Takayuki Katoh, Hiraku Takada.
      Development of genetic code reprogramming methodologies has enabled the ribosomal incorporation of diverse backbone-altering nonproteinogenic amino acids (BAAs)-including d-α-amino acids, β-amino acids, and N-methyl-α-amino acids-into nascent peptides. However, their incorporation is far less efficient than that of canonical l-α-amino acids. We previously demonstrated that the ribosomal E-site-binding translation factors, EF-P and ABC-F proteins, can enhance BAA incorporation. These findings motivated us to investigate additional ribosome-binding factors that might further facilitate this process. Here, we focused on two putative A-site-binding factors, YebC and YeeN, to activate A-site BAA-tRNA and facilitate efficient incorporation. When testing 11 BAAs for consecutive incorporation, YebC and YeeN yielded average enhancements of 2.1- and 2.7-fold, respectively, with an increase of up to 6.6-fold in specific cases. Furthermore, combining YebC with EF-P and Uup (a representative ABC-F protein) produced an 8.0-fold increase in the incorporation of two consecutive N-methyl-l-leucine residues, demonstrating a clear synergistic benefit. We also found that YebC and YeeN promote ribosomal synthesis of drug-like macrocyclic peptides enriched with BAAs, such as d-serine, 1-aminocyclobutane-1-carboxylic acid, N-methyl-l-alanine, and β3-homomethionine. These results pave the way for the ribosomal synthesis of diverse macrocyclic peptide libraries and their application in mRNA display-based screening for novel bioactive compounds.
    DOI:  https://doi.org/10.1093/nar/gkag617
  16. Proc Natl Acad Sci U S A. 2026 Jun 30. 123(26): e2611131123
    MDM2 suppresses c-Myc synthesis by binding to the 5' mRNA translation regulatory sequence.
    Justine Habault, Norman Salomao, Lixiao Wang, Laurence Malbert-Colas, Chrysoula Daskalogianni, Sivakumar Vadivel Gnanasundram, Mitesh Dongre, Marzia Spagnardi, Lucia Martinkova, Sa Chen, Lenka Hernychová, Lucas Robidas, Josef Kucera, Ondřej Bonczek, Daniel Öhlund, Michael J Garabedian, Susan K Logan, Borek Vojtesek, Robin Fahraeus.
      The p53 tumor suppressor and the c-Myc oncogene are among the most frequently deregulated genes in human cancers, yet the molecular cross talk between these pathways remains poorly understood. MDM2 is a key negative regulator of p53 and a target for emerging cancer therapies designed to activate p53. Likewise, targeting c-Myc is a long-standing but challenging goal in cancer therapy. Here, we report that the small MDM2-binding drug Milademetan promotes an interaction between MDM2 and the 5' untranslated region of the c-Myc mRNA, causing a suppression of c-Myc mRNA translation without affecting c-Myc RNA levels. The interaction also occurs under nonproliferative conditions in the absence of drug. Milademetan-mediated c-Myc depletion is accompanied by the induction of apoptosis and suppression of cell proliferation and prevents tumor growth, independently of p53 status. These findings reveal an unexpected mechanism by which MDM2 coordinates two of the most frequently altered pathways in cancer and provide a rationale for targeting c-Myc-driven tumors, including those lacking functional p53, through MDM2 modulators.
    Keywords:  MDM2-RNA interaction; c-MYC; p53; translation control; tumor heterogeneity
    DOI:  https://doi.org/10.1073/pnas.2611131123
  17. Genes (Basel). 2026 May 29. pii: 619. [Epub ahead of print]17(6):
    The Late Evolution of the Nascent Peptide Code for Translational Control and Its Relationship to the Standard Genetic Code.
    Gustavo Caetano-Anollés.
      Background: Recent work has revealed that protein-coding sequences encode regulatory information influencing mRNA stability and translation through a nascent peptide code. However, the evolutionary origin of this regulatory layer remains unclear. This study aims to determine when peptide-mediated translational control emerged during the evolution of the proteome and genetic code. Methods: Dipeptide-specific effects on mRNA stability and translation were integrated with a phylogenetic timeline of dipeptide emergence derived from dipeptide sequences across proteomes. Each of the 400 canonical dipeptides was assigned an evolutionary age, and experimentally derived regulatory effects were mapped onto this timeline, with associations assessed using rank-based correlation and regression analyses. Results: A weak but statistically significant negative association was observed between dipeptide age and mRNA stability, indicating that more recently evolved dipeptides tend to destabilize transcripts. This trend was stronger at the amino acid level, where later-emerging residues showed greater contributions to reduced mRNA levels. Destabilizing effects were associated with physicochemical properties such as positive charge, side-chain bulkiness, and β-strand propensity. Mapping these effects onto codon space revealed a non-random distribution aligned with the evolutionary and structural organization of the genetic code. Destabilizing effects were also enriched within specific codon exchange groups, indicating that regulatory signals are structured within the degeneracy and mutational neighborhoods of the code. Conclusions: These findings indicate that the nascent peptide code is a late evolutionary innovation linked to amino acid expansion and proteomic complexity, with regulation embedded within both peptide sequences and the degeneracy structure of the standard genetic code.
    Keywords:  dipeptides; genetic code evolution; mRNA stability; nascent peptide code; phylogenomics; protein evolution; ribosome dynamics; translational control
    DOI:  https://doi.org/10.3390/genes17060619
  18. Genes (Basel). 2026 May 29. pii: 620. [Epub ahead of print]17(6):
    Transfer RNA (tRNA) Genes, Codon Usage and Translational Efficiency in Leishmania infantum.
    Ariel Nájera-Peso, Andrés Carrazco-Montalvo, Javier Adán-Jiménez, Jose M Requena.
      Background/Objectives: Protozoan parasites of the genus Leishmania are causative agents of a group of devastating human diseases, known as leishmaniasis. These microorganisms possess very unusual mechanisms of gene expression that are poorly understood. This study was aimed at analyzing the tRNA repertoire encoded in the Leishmania infantum genome, a species responsible for the most severe form of disease, visceral leishmaniasis. tRNAs are adaptor molecules aimed at decoding mRNAs into proteins. Results: A total of 92 tRNA genes, dispersed on 38 loci, were identified, often located in regions where unidirectional gene arrays converge. Putative intronic sequences were inferred for three tRNA genes, and, remarkably, nine tRNAs were found to overlap with the protein-coding sequences of annotated genes. According to structural predictions, the L. infantum tRNA repertoire covers 49 out of the 61 possible anticodons, but because of the well-documented wobble phenomenon, these are enough to decode all codons in the 8532 protein-coding genes currently annotated in its genome. As illustrated in this study, codon usage is a well-conserved trait among different Leishmania species but it differs substantially regarding its human host. Finally, we analyzed tRNA adaptation index (tAI) parameters, codon usage metrics, and relative protein expression levels. Conclusions: Apart from providing the tRNA gene repertoire and its genome distribution, we have shown the existence of a statistically significant, positive correlation between the tAI scores and protein expression levels in L. infantum promastigotes.
    Keywords:  Leishmania; codon usage; protein expression; proteome; tRNAs; transfer RNAs
    DOI:  https://doi.org/10.3390/genes17060620
  19. J Biol Chem. 2026 Jun 23. pii: S0021-9258(26)02164-2. [Epub ahead of print] 113292
    An isotype-specific phosphorylation of Hsp90 rewires co-chaperone regulations.
    Tisya Banerjee, Elisabetta Moroni, Maximilian Riedl, Giorgio Colombo, Johannes Buchner.
      The molecular chaperone Hsp90 is a major protein folding factor in the cytosol of eukaryotic cells. Its conformational cycle is regulated by various co-chaperones and post-translational modifications (PTMs) such as phosphorylation. Most of the phosphorylation sites are conserved between the two isoforms of human Hsp90, Hsp90α and Hsp90β. The analysis of the function of these sites has revealed general functional principles of Hsp90. To what extent isoform-specific phosphorylation regulates Hsp90 function is less well understood. Here, we explore the effect of the phosphorylation of a residue (threonine 446) specific for the constitutionally active isoform Hsp90β. Since T446 is bioinformatically predicted to be phosphorylated by kinases regulating the intrinsic stress response (ISR), this modification links Hsp90 function to the ISR status of the cell in an isotype-specific manner which renders Hsp90 unresponsive to the co-chaperone-mediated modulation of its ATPase activity and consequently affects client maturation. Hsp90β reverts to baseline ATPase-driven chaperoning activity which is no longer intensively regulated by co-chaperones and results in the rewiring of Hsp90-mediated protein quality control.
    Keywords:  Molecular chaperones; glucocorticoid receptor; integrated stress response; phosphorylation; posttranslational modification; protein quality control
    DOI:  https://doi.org/10.1016/j.jbc.2026.113292
  20. Curr Opin Cell Biol. 2026 Jun 25. pii: S0955-0674(26)00054-2. [Epub ahead of print]101 102666
    Nuclear determinants of mRNA and protein isoforms.
    Paulina Podszywalow-Bartnicka.
      Isoform generation is a strategy for fine-tuning the activity of essential proteins, particularly during cell differentiation and cancer development. The coding sequence of mRNA is determined by alternative splicing during pre-mRNA processing, allowing the generation of different mRNA variants from a single gene. Alternative splicing is modulated by several pathways, including the selection of transcription initiation and termination sites. The activity of RNA-binding proteins involved in splicing is affected by spatial factors, including RNA folding, separation in local bio-condensates, and the three-dimensional organization of chromatin. The length of untranslated regions and the selection of alternative polyadenylation sites impact mRNA stability and translation accessibility, ultimately controlling the abundance of specific isoforms. This review highlights recent discoveries about the nuclear factors that modify alternative splicing, thereby coordinating the variety of mRNA and protein isoforms with cell state.
    DOI:  https://doi.org/10.1016/j.ceb.2026.102666
  21. Sci Adv. 2026 Jun 26. 12(26): eaed2171
    Single-cell heterogeneity in ribosome levels and protein synthesis during nutrient starvation is driven by cAMP signaling.
    Zhihui Lyu, Jacques Augenstreich, Volker Briken, Abhyudai Singh, Matteo Mori, Terence Hwa, Jiqiang Ling.
      Ribosomes are central to protein synthesis and a frequent target for antibiotics. In fast-growing bacteria, the ribosome content is proportional to the growth rate; how ribosomes and protein synthesis are regulated during nutrient starvation remains poorly understood, particularly in single cells. To address this, we fluorescently labeled ribosomal proteins (RPs) in Salmonella and explored their variations and regulation in single cells. We show that the RP levels become heterogeneous during the transition to the stationary phase. Unexpectedly, cells with higher RP levels responded less to the induction of gene expression but accumulated more virulence gene products. Our work further reveals that adenosine 3',5'-monophosphate (cAMP) signaling increases the heterogeneity of the levels of RPs and other gene products. Fluorescence dilution assay and proteomic analysis indicate that cAMP signaling promotes gene expression heterogeneity by directing proteome-wide adaptation, which enables growth heterogeneity, hence differential dilution of gene products during nutrient depletion.
    DOI:  https://doi.org/10.1126/sciadv.aed2171
  22. bioRxiv. 2026 Jun 10. pii: 2026.06.08.730917. [Epub ahead of print]
    The p97 adaptor p47/NSFL1C is necessary for stress granule dissolution after heat stress.
    Michelle A Johnson, Richa Khanna, Sirisha Mukkavalli, Ly Nguyen, Malavika Raman.
      Stress granules form in response to diverse cellular perturbations to sequester translation components until the stress is resolved. Stress granules are composed of RNA-protein assemblies in membrane delimited structures and must be rapidly disassembled to release components to allow translation to resume. Disassembly of stress granules formed in response to heat stress is dependent on ubiquitiylation of stress granule components such as G3BP1. Ubiquitylation of stress granule proteins recruits the AAA-ATPase p97 (also known as VCP) to enable ubiquitin-dependent disassembly of these structures. Loss of p97 activity leads to the persistence of stress granules and is implicated in several age-related neurodegenerative diseases. Here we show that p97 recruitment to stress granules is dependent on its ubiquitin binding co-factor p47. p47 translocates to stress granules in response to a variety of cellular stressors and is required for the recruitment of p97 to stress granules. Loss of p47 leads to an inhibition in stress granule disassembly. We further show that p47 associates with G3BP1 in response to heat stress in a ubiquitin-dependent manner. Taken together our data adds to the growing list of p97 adaptors that are implicated in the recruitment of p97 for dissolution of stress granules.
    DOI:  https://doi.org/10.64898/2026.06.08.730917
  23. Mol Metab. 2026 Jun 25. pii: S2212-8778(26)00093-1. [Epub ahead of print] 102409
    RNASET2 degrades mRNAs that protect against lipotoxicity.
    Shuiling Zhao, Stevens Bontemps, Ryan M Nottingham, Jun Yao, Mariana Acuña, David E Cohen, Alan M Lambowitz, Jean E Schaffer.
       ABSTRACT/OBJECTIVE: RNASET2 is a lysosomal RNase whose enzymatic function is required for early events in lipotoxicity. However, the endogenous RNA substrates of RNASET2 that modulate lipid-induced cell death are not known. The purpose of this study was to identify RNASET2 substrates that impact lipotoxic stress.
    METHODS: RNA sequencing was used to identify RNAs that increase in abundance in human cells upon RNASET2 knockdown, and actinomycin D assays were used to show that RNASET2 impacted decay rates of these RNAs. We tested for the presence of these RNAs in immunoisolated lysosomes and determined the contribution of the lysosomal membrane transporter SIDT2 in delivery of these RNAs to the lysosome. A role for these RNAs in lipotoxic cell death was directly tested in loss- and gain of function analysis.
    RESULTS: RNASET2 knockdown increased steady-state abundance of UCHL3, PFN2 and PRDX3 mRNAs and prolonged their decay rate, leading to increased protein expression. These mRNAs were delivered to the lysosomal lumen by the lysosomal membrane transporter SIDT2 that mediates RNautophagy. While UCHL3 and PFN2 have not previously been implicated in lipotoxic responses, expression of these proteins protected against lipid-induced cell death.
    CONCLUSIONS: Our study identified specific mRNA substrates of RNASET2 and uncovered a previously unexplored function for lysosomes and RNautophagy in regulation of the response to metabolic stress. Moreover, we demonstrated that RNautophagy selectively regulates turnover of specific endogenous RNAs and thereby impacts regulation of gene expression.
    Keywords:  RNA degradation; autophagy; gene expression; lipotoxicity; lysosomes
    DOI:  https://doi.org/10.1016/j.molmet.2026.102409
  24. Nature. 2026 Jun 24.
    Alternate RNA decoding results in stable and abundant proteins in mammals.
    Shira Tsour, Rainer Machné, Andrew Leduc, Simon Widmer, Eunice Koo, Jeremy Guez, Konrad J Karczewski, Nikolai Slavov.
      Amino acid substitutions may substantially alter protein stability and function1,2. However, the contribution of substitutions that arise from alternate translation (deviations from the genetic code) is unknown. Here to address this issue, we analysed deep proteomic, transcriptomic and genomic data from more than 1,000 human samples, including 6 cancer types and 26 healthy human tissues. This global analysis identified 60,803 fragmentation spectra corresponding to 8,746 unique substitutions in proteins derived from 1,767 genes, including 1,955 confidently localized sites. Some substitutions were shared across samples, whereas others exhibited strong tissue-type and cancer specificity. Notably, products of alternate translation were more abundant than their canonical counterparts for hundreds of proteins, which suggests that there is sense-codon recoding. Recoded proteins included transcription factors, proteases, signalling proteins and proteins associated with neurodegeneration. Mechanisms that contribute to substitution abundance included protein stability, codon frequency, codon-anticodon mismatches and RNA modifications. We also characterized how alternatively translated proteoform ratios vary across protein domains, tissue types and cancers. These ratios were positively associated with intrinsically disordered regions and genetic polymorphisms in the gnomAD database, although the polymorphisms could not account for the substitutions. The sequence, relative abundance and the tissue specificity of alternatively translated proteins were conserved between humans and mice. These results demonstrate the contribution of alternate translation to the diversification of mammalian proteomes and its association with protein stability, tissue-specific proteomes and disease.
    DOI:  https://doi.org/10.1038/s41586-026-10678-2
  25. ArXiv. 2026 Jun 13. pii: arXiv:2606.12219v2. [Epub ahead of print]
    m6A-FORM: An m6A-focused Foundation Model for Decoding m6A Regulatory Function.
    Ting-He Zhang, Sumin Jo, Shou-Jiang Gao, Yufei Huang.
      N6-methyladenosine (m6A) regulates mRNA fate through site-specific methylation, reader recognition and downstream effects on RNA stability and decay. However, current computational approaches focus mainly on site prediction, leaving unresolved the broader challenge of inferring m6A regulatory context and function from epitranscriptomic profiles. Here we present m6A-FORM, an m6A-focused foundation model for for regulatory discovery. Pretrained on 24.9 million RNA sequence windows from 22.5 million MeRIP-seq regions across 143 human studies, m6A-FORM learns reusable representations of m6A-associated transcript contexts. We adapt this encoder to single-nucleotide m6A discovery, regulator-binding prediction, YTHDF2-associated decay prediction and tissue-scale epitranscriptomic mapping. m6A-FORM predicts binding of 19 m6A readers, writers and erasers and identifies sequence and RBP-context features associated with YTHDF2-mediated RNA degradation. Applied to 67 datasets from 24 human tissues, it identifies tissue-conserved m6A sites linked to stronger methylation, reader binding, RBP occupancy and decay propensity.
  26. Plants (Basel). 2026 Jun 10. pii: 1790. [Epub ahead of print]15(12):
    Target of Rapamycin Coordinates Metabolic Remodeling at the Protein Level in the Red Alga Cyanidioschyzon merolae.
    Jyothi Priya Putcha, Sousuke Imamura.
      Target of rapamycin (TOR) is a conserved protein kinase that integrates nutrient and energy signals to control growth and metabolism, yet its proteome-level impact in microalgae remains poorly understood. Here, we conducted quantitative proteomics analysis of the unicellular red alga Cyanidioschyzon merolae under rapamycin-induced TOR inactivation to characterize global changes in protein abundance. TOR inhibition triggered widespread metabolic remodeling, including coordinated shifts in carbon and nitrogen allocation, and pronounced changes in protein synthesis, photosynthesis, and energy metabolism. Specifically, proteins associated with ribosome biogenesis and ribosomal subunits declined broadly, indicating impaired translation, alongside pronounced reductions in photosynthetic components, including PSI/PSII subunits and chlorophyll biosynthesis enzymes. In contrast, triacylglycerol (TAG) biosynthesis and starch metabolism were enhanced, indicating a shift towards carbon storage. Notably, a diacylglycerol acyltransferase (DGAT; CMQ199C) and a UDP-glucose pyrophosphorylase (UGP; CMS159C) were strongly induced (2.02-fold and 3.48-fold, respectively), identifying them as candidate targets for enhancing TAG and starch accumulation. Proteins associated with nitrogen assimilation were also upregulated, supporting TOR-dependent regulation of nitrogen metabolism at the protein level. Together, these results indicate that TOR orchestrates proteome-level reprogramming in C. merolae, coordinating growth, energy production, and carbon storage across interconnected metabolic pathways.
    Keywords:  Cyanidioschyzon merolae; microalgae; proteomics; red alga; starch; target of rapamycin; triacylglycerol
    DOI:  https://doi.org/10.3390/plants15121790
  27. Cells. 2026 Jun 18. pii: 1106. [Epub ahead of print]15(12):
    Beyond Hydrogen Sulfide and Cysteine Metabolism: Reframing Cystathionine γ-Lyase as a Potential Translational Regulator of Hypoxia-Inducible Factor-1α in Clear Cell Ovarian Carcinoma.
    Amal M El-Naggar.
      The canonical transsulfuration (TSS) pathway enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH) are traditionally recognized for their roles in the sequential conversion of homocysteine to cysteine and in endogenous hydrogen sulfide (H2S) production. Increasing evidence, however, suggests that these enzymes may also exhibit non-canonical ("moonlighting") functions that extend beyond metabolic regulation. In this review, we evaluate the hypothesis that CTH may participate in translational regulation, particularly in the control of hypoxia-inducible factor-1α (HIF-1α) expression in clear cell ovarian carcinoma (CCOC). We first highlight limitations of the prevailing H2S- and cysteine-centric view of the TSS pathway, which may not fully explain emerging context-dependent functions of CTH in cancer biology. Current evidence suggests that CTH enhances HIF-1α protein expression through mechanisms independent of transcription, protein stability, or H2S production, implicating a potential role in translational regulation, although direct mechanistic evidence remains limited. To critically evaluate this emerging hypothesis, we categorize evidence according to its level of experimental support, ranging from direct experimental evidence to indirect mechanistic observations and computational predictions. Within this framework, we examine three non-mutually exclusive models: (1) regulation through PI3K/AKT/mTOR-dependent translational signaling; (2) modulation of translational control through interaction with translation-associated proteins and RNA-binding proteins (RBPs) involved in HIF1A mRNA regulation; and (3) the more speculative possibility of direct interaction between CTH and HIF1A mRNA. Collectively, these observations support a model in which CTH contributes to selective translational regulation beyond its canonical metabolic functions, potentially linking sulfur metabolism to stress-adaptive gene expression in cancer.
    Keywords:  CTH; HIF-1α; RNA-binding proteins; clear cell ovarian carcinoma; cysteine biosynthesis; hydrogen sulfide; moonlighting functions; translation regulation
    DOI:  https://doi.org/10.3390/cells15121106
  28. Curr Drug Targets. 2026 Jun 19.
    Epitranscriptomics in Breast Cancer: The Unveiled Role of RNA Modifications.
    Pallavi Kumari, Sanjay Kumar.
      Epitranscriptomics, the study of dynamic chemical modifications on RNA molecules, has emerged as a pivotal layer of gene expression regulation with profound implications for cancer biology. This review centers on three well-characterized RNA modifications, N6-methyladenosine (m6A), pseudouridine (Ψ), and 5-methylcytosine (m5C), and highlights their diverse roles in the pathogenesis of breast cancer. These modifications modulate critical post-transcriptional processes such as RNA splicing, stability, translation, and degradation, thereby influencing tumor initiation, progression, metastasis, therapy resistance, and interactions within the tumor microenvironment. Also the study briefly explores emerging modifications, including Adenosine-to-Inosine (A-to-I) editing and N1-methyladenosine (m1A), which add further complexity to the epitranscriptomic landscape. Advances in high-throughput sequencing, bioinformatics, and single-cell technologies have significantly deepened understanding of the context-dependent and reversible nature of these modifications. Importantly, RNA modification signatures show promise as non-invasive biomarkers and therapeutic targets. However, translating these insights into clinical applications remains challenging due to issues related to delivery mechanisms, specificity, and regulatory hurdles. This review provides a comprehensive synthesis of current knowledge, highlights key controversies and technological limitations, and discusses future directions for leveraging epitranscriptomics in the early detection and personalized treatment of breast cancer.
    Keywords:  Epitranscriptomics; RNA modification diagnostics.; RNA modification therapy; RNA modifications
    DOI:  https://doi.org/10.2174/0113894501456782260615073934
  29. J Biol Chem. 2026 Jun 23. pii: S0021-9258(26)02161-7. [Epub ahead of print] 113289
    CCR4-NOT is required for suppressing pervasive transcription and retrotransposable elements.
    Shardul D Kulkarni, Alexis Morrissey, Aswathy Sebastian, Oluwasegun T Akinniyi, Cheryl A Keller, Istvan Albert, Shaun Mahony, Joseph C Reese.
      CCR4-NOT regulates multiple steps in gene regulation and has been well studied in yeast. While the human complex is known to play an essential role in cytoplasmic mRNA degradation, its nuclear functions are poorly characterized. Here, we used auxin-induced degradation to deplete the scaffold subunit CNOT1 and the E3 ligase CNOT4 to characterize the complex's regulation of transcription. Transient transcriptome profiling (TT-Seq) revealed that depleting either subunit led to widespread activation of RNA synthesis in genic and intergenic regions. Interestingly, fewer genes were down-regulated, including KRAB-Zinc-Finger-protein (KZNF) genes. KZNFs repress genes and retrotransposable elements (rTEs), and consistent with decreased KZNF expression, rTEs, mainly Long Interspersed Nuclear Elements (LINEs), were activated. Full-length active LINEs and rTEs located outside of genes were activated too, suggesting that the increased transcription is not the direct result of transcription of the genes in which the rTEs are embedded. Most of the activated transcription events occurred near KZNF binding sites, suggesting that KZNF regulation plays a role in suppressing both genic and rTE transcription. Finally, we demonstrate that CCR4-NOT regulates the stability of rTE RNAs, indicating that the complex tightly controls transposon expression by repressing transcription and targeting their RNAs for degradation.
    Keywords:  CCR4-NOT; Krab Zinc finger proteins (KZFPs); Retrotransposons; Transcription
    DOI:  https://doi.org/10.1016/j.jbc.2026.113289
  30. Amino Acids. 2026 Jun 26.
    Dual functions of thermospermine in plant growth and stress responses.
    Valerio Foschi, Riccardo D'Incà, Mitsuru Saraumi, Paraskevi Tavladoraki, Taku Takahashi.
      In seed plants, putrescine, spermidine, and spermine are ubiquitously present, whereas a structural isomer of spermine, thermospermine (TSpm), is synthesized mainly in the vascular tissue. Initially identified in the bacterium Thermus thermophilus, TSpm was later shown to be synthesized in Arabidopsis thaliana by ACAULIS5 (ACL5). ACL5 gene homologs may have been acquired early in plant evolution via endosymbiotic gene transfer from a cyanobacterial ancestor. Loss-of-function acl5 mutants exhibit a dwarf phenotype and excessive vascular xylem formation. Subsequent studies, including analysis of suppressor-of-acl5 (sac) mutants, revealed that TSpm exerts a critical role in the repression of vascular xylem proliferation by acting in upstream open-reading-frame (uORF)-dependent translational regulation of specific mRNAs. A recent study revealed functional TSpm binding to the peptidyl transferase center of 25 S rRNA promoted by methylation of residue U2952. Like other polyamines, TSpm has also been shown to participate in stress responses, enhancing tolerance to salt, drought, heat, and pathogen challenges in multiple species. Collectively, TSpm represents a unique polyamine with dual roles in xylem development and stress adaptation, whose evolutionary origin and molecular mechanisms provide insights into the specialization of polyamine biology. Further studies in nonvascular plants and algae are needed to elucidate the ancestral functions of TSpm.
    Keywords:   Arabidopsis ; RNA modification; Thermospermine; Xylem development; mRNA translation; uORF
    DOI:  https://doi.org/10.1007/s00726-026-03533-1
  31. Biomedicines. 2026 Jun 11. pii: 1330. [Epub ahead of print]14(6):
    Modulation of Stress and Anabolic Signalling Pathways by Whey Protein Isolate in C2C12 Cells Under Exercise-Mimetic Conditions.
    Simone Mulè, Rebecca Galla, Matteo Musu, Francesca Parini, Francesca Uberti.
      Background/Objectives: Skeletal muscle adaptation to metabolic stress involves a coordinated regulation of inflammatory, bioenergetic, and anabolic signalling pathways. This study aimed to investigate the potential role of whey protein isolate (WPI; commercial name: Volapure) as a modulator of cellular responses to stress in an in vitro model of exercise-mimetic stress over time. Methods: Murine C2C12-differentiated cells were exposed to an Exercise-Mimetic Mix (ExM) to reproduce key biochemical features of muscle stress. Cells were treated with WPI (1 mg/mL) using Pre-exposure (Pre-ExM) and Post-exposure (Post-ExM) protocols at 8 and 24 h. Multiple endpoints were assessed, including cell viability, reactive oxygen species (ROS) production, cytokine release (TNF-α, IL-6, IL-17), intracellular signalling pathways (p38 MAPK, ERK, AMPK, mTOR), bioenergetic markers (ATP, glycogen, lactate), protein synthesis (OPP incorporation), and Ca2+/Mg2+ fluxes. Results: ExM exposure induced a stress phenotype characterised by increased oxidative and inflammatory markers, impaired bioenergetic status, and reduced anabolic signalling. WPI was associated with modulation of these responses, reducing ROS and pro-inflammatory cytokines, restoring ATP and glycogen levels, and changes in ERK and mTOR-related signalling. The Post-ExM protocol showed greater modulation compared to the Pre-ExM approach, particularly at 24 h. WPI was also associated with the normalisation of ExM-altered Ca2+/Mg2+ fluxes. These findings should be interpreted as associative rather than causal. Conclusions: WPI was associated with modulation of key pathways involved in cellular adaptation to metabolic stress, supporting recovery of bioenergetic balance and anabolic signalling in C2C12 cells. These findings suggest a potential role for WPI in influencing cellular responses to metabolic stress, supporting recovery of bioenergetic balance and anabolic signalling in C2C12-differentiated-cells. However, further studies are required to confirm the translational relevance of these observations.
    Keywords:  C2C12 cells; anabolic signalling; bioenergetics; cellular stress response; exercise-mimetic stress; mTOR pathway; myokines; oxidative stress; skeletal muscle; whey protein isolate
    DOI:  https://doi.org/10.3390/biomedicines14061330
  32. Annu Rev Cell Dev Biol. 2026 Jun 25.
    mRNA-Scaffolded Cytoplasmic Compartments.
    Christine Mayr.
      The cytoplasm of vertebrate cells is compartmentalized into the cytosol and several messenger RNA (mRNA)-scaffolded condensates, present at steady-state conditions and in the absence of stress. They include TIS granules and the FXR1 network and act as translation, folding, and signaling environments. Therefore, in addition to serving as templates for protein synthesis, mRNAs play essential roles in cytoplasmic organization. However, not all mRNAs function as condensate scaffolds. Whereas mRNAs with short and structured 3' untranslated regions (UTRs) usually diffuse freely and localize to the cytosol, scaffold mRNAs are characterized by long and multivalent 3' UTRs. Scaffold mRNAs are responsible for the characteristic irregular, network-like morphology of mesh-like condensates and play active, functional roles during protein biosynthesis. For example, mesh-like condensates act as folding environments for proteins with long intrinsically disordered regions, where multivalent 3' UTRs act as cotranslational chaperones to prevent protein misfolding. The scaffold function of mRNAs is also important for post-translational processes, where the mRNA-mediated proximity of signaling factors promotes cellular signaling reactions. In this review, the discovery of cytoplasmic mRNA-scaffolded mesh-like compartments and their currently known assembly principles and biological roles are discussed.
    DOI:  https://doi.org/10.1146/annurev-cellbio-111524-021431
  33. RNA. 2026 Jun 24. pii: rna.080960.126. [Epub ahead of print]
    Reduced Sensitivity to RNA Structural Differences Distinguishes Eukaryotic Pus4 from Bacterial TruB.
    Amelia S Cochran, David Muzyka, Jacqueline Anthenien, Fiona Tillyer, Markos Koutmos, Kristin S Koutmou.
      Pseudouridine is an abundant post-transcriptional modification important to RNA structure and function. The isomerization of uridine (U) to pseudouridine (Ψ) is catalyzed by members of the pseudouridine synthase (Pus) family throughout all domains of life. All Pus enzymes modify non-coding RNAs, and a subset also pseudouridylate protein-coding messenger RNAs (mRNAs). Although the precise role of Ψ in mRNAs remains to be established, emerging evidence suggests that Ψ might contribute to the post-transcriptional control of gene expression. However, the mechanisms driving mRNA target selection by individual Pus enzymes still need to be defined. The bacterial Pus enzyme TruB has been well characterized and modifies tRNA at position U55 within T-loops. In addition to catalyzing Ψ55 in most tRNAs, eukaryotic TruB orthologs also pseudouridylate mRNAs. While it has been proposed that eukaryotic TruB orthologs modify mRNA at sites that mimic their tRNA targets in sequence and secondary structure, only a fraction of such sites are pseudouridylated in cells. Here, we demonstrate that the Saccharomyces cerevisiae TruB ortholog Pus4 binds and modifies RNAs that differ in secondary structure from its established tRNA substrates in vitro. Comparison of Pus4 and TruB activities on structurally diverse substrates reveals that while both enzymes can modify a variety of substrates, TruB does do less robustly than Pus4. We also find that the bacterial-specific PUA domain modulates TruB substrate selection. These findings are consistent with reports demonstrating that other mRNA-modifying Pus enzymes are more promiscuous in vitro than in cells. Our results suggest that Pus4 substrate selection might rely on additional factors beyond protein-RNA recognition in cells.
    Keywords:  Pus4; RNA modification; TruB; pseudouridine; pseudouridine synthase
    DOI:  https://doi.org/10.1261/rna.080960.126
  34. Biomolecules. 2026 Jun 11. pii: 858. [Epub ahead of print]16(6):
    m6A RNA Methylation-miRNA Crosstalk in Cardiovascular Remodeling.
    Liujie Long, Yi Yang, Chufang Zheng, Kang Kang.
      Cardiovascular remodeling, encompassing vascular remodeling, myocardial remodeling, and fibrosis-associated tissue remodeling, underlies atherosclerosis, pulmonary hypertension, myocardial infarction, myocardial fibrosis, and other cardiovascular diseases. Its regulation has traditionally been studied through transcriptional, inflammatory, metabolic, mechanical, and intercellular signaling mechanisms. Recent advances in epitranscriptomics have identified N6-methyladenosine (m6A) RNA methylation as an additional post-transcriptional layer that interacts with microRNA (miRNA) pathways during cardiovascular disease progression. This review summarizes current evidence for m6A-miRNA crosstalk in cardiovascular remodeling, focusing on epitranscriptomic checkpoints that regulate miRNA fate, feedback-like regulatory circuits involving miRNAs and the m6A machinery, and cell-type-specific programs across endothelial cells, vascular smooth muscle cells, fibroblasts, and cardiomyocytes. We further discuss emerging analytical technologies and translational implications of this regulatory axis. Future studies should clarify causal mechanisms, cell-type and disease-stage specificity, and translational feasibility. Together, this multilayered framework provides a systems-level perspective on how RNA regulatory networks may shape pathological remodeling in cardiovascular disease.
    Keywords:  cardiomyocytes; cardiovascular disease; endothelial cells; epitranscriptomics; extracellular vesicles; fibroblasts; m6A; non-coding RNAs; vascular remodeling; vascular smooth muscle cells
    DOI:  https://doi.org/10.3390/biom16060858
  35. Front Cell Dev Biol. 2026 ;14 1814142
    Epigenetic regulation of cuproptosis in cancer: mechanisms, microenvironment, and therapeutic implications.
    Xin Zhang, Yixiao Yuan, Lin Tang, Juan Wang, Lincan Duan, Xiulin Jiang, Jia Zhang.
      Cuproptosis is a regulated form of cell death triggered by copper overload and dependent on mitochondrial metabolism, particularly through FDX1-mediated protein lipoylation and TCA cycle disruption. Recent studies have revealed that epigenetic mechanisms, including DNA methylation, histone modifications, non-coding RNAs, and RNA chemical modifications such as m6A and lactylation, critically regulate the expression of copper transporters, lipoylation enzymes, mitochondrial metabolic proteins, and stress response pathways, thereby modulating tumor cell susceptibility or resistance to cuproptosis. For example, DNA methylation can control copper homeostasis genes through a DNMT/miRNA/copper transporter axis, while histone lactylation links metabolic rewiring to copper accumulation. Non-coding RNAs and RNA modifications fine-tune the transcription and translation of key cuproptosis regulators, providing dynamic control over cell fate. The tumor microenvironment (TME) further influences cuproptosis by shaping copper availability, redox status, hypoxia, and metabolic reprogramming, and interacts with immune surveillance and PD-1/PD-L1 signaling. Translationally, copper ionophores, nanomedicine-based delivery systems, and combination strategies targeting both metabolic vulnerabilities and the TME offer promising approaches to induce tumor-specific cuproptosis while minimizing toxicity. Overall, the integration of molecular, epigenetic, and microenvironmental regulation in cuproptosis provides new insights into tumor metabolic vulnerabilities and offers potential targets for precision anticancer therapies.
    Keywords:  FDX1; TCA cycle; cancer therapeutics; copper metabolism; cuproptosis; metal homeostasis; mitochondrial cell death; proteotoxic stress
    DOI:  https://doi.org/10.3389/fcell.2026.1814142
  36. Int J Mol Sci. 2026 Jun 18. pii: 5512. [Epub ahead of print]27(12):
    Alternative Splicing in Plant Development and Abiotic Stress Responses: A Multifunctional Regulatory Mechanism.
    Hye-Yeon Seok, Sun-Young Lee, Dahyun Kim, Yong-Hwan Moon.
      Alternative splicing (AS) is a major post-transcriptional regulatory mechanism that greatly expands transcriptomic and proteomic diversity in plants. Recent studies have demonstrated that AS dynamically regulates gene expression during plant development and under diverse environmental conditions through isoform-specific modulation of transcript stability, translation efficiency, protein localization, and signaling pathways. In this review, we summarize recent advances in understanding the roles of AS in plant development and abiotic stress responses. Mechanistically, splice site selection is regulated through coordinated interactions among cis-regulatory elements, RNA-binding proteins, RNA secondary structures, transcriptional kinetics, chromatin organization, and spliceosomal dynamics. AS plays critical roles in various developmental processes, including seed germination, vegetative growth, flowering transition, and senescence, while also contributing to plant adaptation to abiotic stresses such as osmotic, temperature, and oxidative stresses. Particular emphasis is placed on the diverse regulatory outcomes of AS, including isoform-specific protein functions, AS-coupled nonsense-mediated decay, transcript stability control, and context-dependent isoform switching. We further discuss the varying levels of experimental evidence supporting reported AS events, ranging from transcriptome-wide observations to genetically and biochemically validated isoform functions. Moreover, recent advances in long-read sequencing, single-cell transcriptomics, proteogenomics, and genome-engineering technologies are accelerating the functional characterization of splice isoforms and uncovering the complexity of AS-mediated regulatory networks. Collectively, these advances highlight AS as a central mechanism coordinating plant developmental plasticity and environmental adaptation.
    Keywords:  abiotic stress; alternative splicing; developmental regulation; plant; splice isoform
    DOI:  https://doi.org/10.3390/ijms27125512
  37. Blood. 2026 Jun 23. pii: blood.2025032484. [Epub ahead of print]
    Translational Regulation of Sf1 Integrates Alternative Splicing and Hematopoietic Stem Cell Fate.
    Vladyslava Liudkovska, Martyna Ciołek, Daniel Grygorowicz, Ankita Kumari, Sandra Irena Binias, Jan Mikołajczyk, Anna M Lenkiewicz, Anna Konturek-Ciesla, Agata Szade, Bartosz Wojtas, Remigiusz Serwa, Tomasz W Turowski, David Bryder, Krzysztof Szade, Maciej Ciesla.
      The transition of hematopoietic stem cells (HSCs) from quiescence to lineage commitment requires precise post-transcriptional control, yet the contribution of mRNA isoform regulation remains poorly defined. Here, we identify a translationally controlled splicing program that contributes to HSC fate decisions. Using activity-based signatures of 305 splicing regulators, we uncover widespread post-transcriptional modulation of the spliceosome in stem and progenitor cells. The branch-point recognition factor Sf1 emerges as a key node, regulated by a conserved structured 5' UTR that cooperates with the RNA-binding protein Igf2bp2 to control its translation. Disrupting this cis-trans module reduces Sf1 protein synthesis and skews differentiation toward stem and erythroid programs. Mechanistically, Sf1-dependent alternative splicing remodels 5' UTRs of hematopoietic and DNA damage response genes, altering their translation and modulating DNA damage resolution. Together, these findings reveal an unrecognized translational layer controlling spliceosome activity and link RNA regulons, alternative splicing, and HSC fate determination.
    DOI:  https://doi.org/10.1182/blood.2025032484
  38. Pharmacol Res. 2026 Jun 20. pii: S1043-6618(26)00227-6. [Epub ahead of print]230 108312
    Targeting RNA quality-control defects in tauopathies: Pharmacodynamic biomarkers and therapeutic development.
    Min Zhang, Aifang Cheng.
      Tau-directed therapies can achieve biochemical target engagement without delivering consistent clinical benefit, suggesting that a key bottleneck in tauopathy development lies not only in target access, but in whether tau engagement leads to measurable recovery of disease-relevant cellular states. Recent studies increasingly link tau-associated dysfunction to RNA abnormalities in surveillance, compartmentalization and stress responses. These findings position RNA quality control as both a downstream consequence of tau pathology and a co-development layer, with potential therapeutic relevance in selected contexts. Here, we frame RNA quality control as a development-oriented layer of dysfunction in tauopathies. Within this layer, nonsense-mediated decay currently shows the strongest intervention-linked evidence, whereas nucleocytoplasmic transport and condensate reversibility are better viewed as biologically supported readout and assay-development domains. We further outline compact pharmacodynamic biomarkers and a framework for matching therapeutic modality to mechanism. By positioning RNA-state measurements as a readout layer and RNA-state correction as a potential intervention layer, this framework may help explain why biochemical tau engagement can produce heterogeneous biological responses and improve the interpretability of tau-directed therapeutic development.
    Keywords:  Nonsense-mediated decay; Nucleocytoplasmic transport; Pharmacodynamic biomarkers; RNA quality control; RNA-protein condensates; Tauopathies; Therapeutic development
    DOI:  https://doi.org/10.1016/j.phrs.2026.108312
  39. Cells. 2026 Jun 20. pii: 1117. [Epub ahead of print]15(12):
    The Interplay of Splicing and Metabolism in Cancer.
    Dillon M Voss, Yange Cui, Peter S Klein.
      Aberrant RNA splicing and metabolic reprogramming are defining hallmarks of cancer that were historically studied as parallel processes. Increasing evidence now reveals extensive crosstalk between these pathways, whereby RNA splicing reshapes metabolic circuits, and metabolic states reciprocally influence splice-site selection and spliceosome activity. In this review, we synthesize recent mechanistic insights into how splicing programs regulate metabolic adaptation across diverse cancer contexts. We discuss recurrent oncogenic mutations in spliceosomal components and dysregulation of RNA-binding proteins (RBPs) that drive alternative splicing events in key metabolic regulators, which promote metabolic plasticity required for tumor growth. We further examine how metabolites and nutrient-sensing pathways directly modulate splicing factor activity, spliceosome dynamics, and RNA processing. We also summarize a new mechanism of mitochondrial quality control mediated by retrograde signals from mitochondria to the spliceosome to enhance mitophagy of dysfunctional mitochondria.
    Keywords:  PINK1; cancer; leukemia; metabolism; mitophagy; myelodysplasia; pyruvate kinase; retrograde signaling; spliceosome; splicing
    DOI:  https://doi.org/10.3390/cells15121117
  40. J Mol Biol. 2026 Jun 24. pii: S0022-2836(26)00286-X. [Epub ahead of print] 169913
    UPF1 at Work: Structural and Mechanistic Insights into a Master Regulator of Nonsense-Mediated mRNA Decay.
    Vincent Mocquet, Francesca Fiorini.
      RNA helicases are central architects of ribonucleoprotein (RNP) organization, coupling nucleoside triphosphate hydrolysis to RNA binding to unwind duplexes, translocate along nucleic acids, displace RNA-binding proteins, and remodel RNP assemblies. Among them, UPF1 (UP-Frameshift 1) is a highly conserved superfamily 1 (SF1) helicase and the pivotal effector of nonsense-mediated mRNA decay (NMD). UPF1 harbors the canonical helicase core motifs required for ATP binding and hydrolysis, RNA interaction, and chemo-mechanical coupling, as well as regulatory domains that fine-tune its catalytic activity and protein-protein interactions. UPF1 displays remarkable enzymatic versatility, acting as an RNA translocase, helicase and RNPase. Its capacity to coordinate these distinct but interconnected activities enables dynamic remodeling of messenger RNPs and positions UPF1 as a multifunctional regulator of RNA fate during NMD. In this review, we integrate current structural and mechanistic insights into UPF1 function and propose a unifying framework that links its biochemical properties to its diverse cellular roles, aiming to reconcile the existing models that describe its mechanism of action.
    Keywords:  ATP binding; ATP hydrolysis; Helicase; Translocase; UPF1
    DOI:  https://doi.org/10.1016/j.jmb.2026.169913
  41. Physiology (Bethesda). 2026 Jun 26.
    RNA-Protein complexes and their role in cell fate.
    Kaito Masaki, Malvin Leonardo Pardi, Hirohide Saito.
      RNA-protein interaction forms an important part of gene expression control in the form of post-transcriptional regulation. It affects key cellular processes, including cell fate-determining events such as self-renewal and differentiation of stem cells, stress response, and senescence. In this review, we present a discussion of RNA-protein complexes as biological continuum between the two ends of traditional, defined stoichiometric assemblies such as ribosomes, spliceosomes, and microRNA-induced silencing complexes (miRISCs) and non-stoichiometric biomolecular condensates such as stress granules, processing bodies, and germ granules, and how the two ends of the spectrum are connected through RNA-protein interactions and RNA modification. We also present how abnormalities in these processes lead to the development of pathological conditions. Finally, we touch upon the remaining unresolved questions in the field, as well as novel experimental approaches to address these questions, which may lead to novel therapeutic opportunities.
    Keywords:  Cell fate transition; RNA-protein complex; RNP complex
    DOI:  https://doi.org/10.1152/physiol.00018.2026
  42. Nucleic Acids Res. 2026 Jun 08. pii: gkag575. [Epub ahead of print]54(11):
    Antisense RNA controls the degradation of phycobilisomes in heterocyst-forming cyanobacteria by a transcriptional interference mechanism.
    Isidro Álvarez-Escribano, Manuel Brenes-Álvarez, Jens Georg, Agustín Vioque, Alicia M Muro-Pastor.
      Transcriptional interference is rarely documented in bacteria. In cyanobacteria, phycobilisomes are the major light-harvesting antennae, and their degradation under non-optimal conditions follows a tightly regulated genetic program leading to the production of NblA, a widely conserved proteolytic adapter. NblA production is regulated at both the transcriptional and post-transcriptional levels. Here, we uncover an additional regulatory layer mediated by an antisense RNA conserved in heterocyst-forming cyanobacteria. In Nostoc sp. PCC 7120, transcription of the abundant antisense RNA (as_nblA) limits nblA mRNA accumulation. A strain unable to transcribe as_nblA produces an excess of NblA, ultimately so harmful that suppressor mutations of nblA expression accumulate rapidly, underscoring the essential role of as_nblA. Rifampicin time-series experiments and the inability of as_nblA to regulate nblA expression in trans support transcriptional interference as the primary regulatory mechanism of as_nblA. Mathematical modeling of nblA expression, supported by biological data, shows that as_nblA plays a pivotal role in preventing leaky nblA expression under non-inducing conditions. Our work highlights the importance of antisense RNA-mediated regulation, particularly transcriptional interference, in establishing thresholds that prevent spurious expression of genes encoding critical cellular functions.
    DOI:  https://doi.org/10.1093/nar/gkag575
  43. Microlife. 2026 ;7 uqag021
    Predicted bacterial uRBSs reveal translational coupling and ribosome-mediated RBS occlusion as gene-controlling mechanisms.
    Theresa Dietz, Julian M Hahnfeld, Sophie Neumann, Yonca A Reinsch, Tessa Wenz, Susanne Barth-Weber, Jochen Blom, Alexander Goesmann, Elena Evguenieva-Hackenberg.
      Upstream open reading frames (uORFs) in the 5' leader of bacterial mRNAs can modulate gene expression, yet genome-wide identification remains limited. We combined bioinformatic prediction of ribosome-binding sites (RBSs)-a Shine-Dalgarno sequence and a start codon-with experimental validation to uncover new uORFs in Sinorhizobium meliloti 2011. From totally 1106 predicted upstream RBSs (uRBSs), we first examined 15 candidates using eGFP reporters and integrating existing RNA-seq and Ribo-seq data. Translation was detected at 13 sites, with fluorescence intensity broadly correlating with predicted initiation rates. Two uRBSs correspond to gene start sites, thereby refining gene annotations. In nine cases, uRBS mutations affected downstream gene expression in reporter fusions. Among others, the data suggests that a Type I secretion system operon, the RNA chaperone gene hfq, and metabolic genes are regulated by uORFs. Four uORFs acted through translational coupling. We also identified uRBSs that were ribosome-occupied yet (nearly) silent in eGFP assays, and closely spaced to the downstream main RBS (mRBS). These uRBSs probably mediate ribosomal occlusion downregulating lacR and SM2011_RS36230. A re-screen of the prediction set revealed 335 close uRBS/mRBS pairs. Three of them were analyzed, supporting the proposed ribosomal occlusion mechanism for SM2011_RS03630 and SM2011_RS22110, while for glnK translational coupling to an uORF was suggested. These results indicate that uORFs are more widespread in bacteria than previously recognized and suggest that direct ribosomal occlusion of the mRBS is a novel mechanism for down-regulating protein synthesis.
    Keywords:  Sinorhizobium meliloti; alphaproteobacteria; mRNA leader; ribosome binding site occlusion; small open reading frame; translational coupling; upstream Shine–Dalgarno sequence; upstream open reading frame; upstream ribosome binding site
    DOI:  https://doi.org/10.1093/femsml/uqag021
  44. G3 (Bethesda). 2026 Jun 22. pii: jkag141. [Epub ahead of print]
    Heat stress reveals bidirectional cross talk between the heat shock response and UPRER in C. elegans.
    Athena Alcala, Toni Castro Torres, Rebecca Aviles Barahona, Phillip A Frankino, Ryo Higuchi-Sanabria, Gilberto Garcia.
      Organisms rely on coordinated stress responses to maintain cellular homeostasis. Perhaps the best-known example of multiple stress inputs converging onto a single response is the integrated stress response, which reduces global translation under various stressed conditions to reduce the protein folding burden of the cell. Similarly, most stress responses generally involve coordination of additional protein homeostasis (proteostasis) pathways, including increased expression of chaperones to refold proteins, as well as activation of clearance mechanisms, such as autophagy and the ubiquitin proteasome system. Our study investigates how heat stress can influence coordinated activation of both cytosolic and endoplasmic reticulum (ER) chaperones, exploring bidirectional cross talk between canonical activators of the cytosolic heat-shock response (HSR) and the unfolded protein response of the ER (UPRER). Using robust transcriptional reporters in the Caenorhabditis elegans model system, we explore a noncanonical activation of the UPRER under heat stress by the coordinated effects of XBP-1 and HSF-1. We further investigate inter-tissue communications of stress whereby neuronal or glial activation of the UPRER can result in heterotypic enhancement of the HSR in peripheral cells and can increase thermotolerance. This work highlights the complex convergence of cellular stress responses, a phenomenon that may reflect a general strategy wherein localized stress can activate numerous proteostasis pathways to prevent whole-cell and whole-organism damage.
    Keywords:  endoplasmic reticulum unfolded protein response; heat stress; heat-shock response
    DOI:  https://doi.org/10.1093/g3journal/jkag141
  45. Med Oncol. 2026 Jun 27. pii: 204. [Epub ahead of print]43(8):
    The translational roles of circular RNAs in cancers and their underlying molecular mechanisms.
    Xinxin Wu, Xiaohan Ye, Huiling Chen, Tao Li, Jiaxin Ge, Jie Guo.
      Circular RNAs (circRNAs) are a class of endogenous RNAs characterized by a covalently closed circular structure. They can be divided into nuclear-encoded circRNAs (nuc-circRNAs) and mitochondria-encoded circular RNAs (mecciRNAs). For the nuc-circRNAs, there are exonic circular RNA (EcircRNA), circular intronic RNA (CiRNA), and exon-intron circular RNA (EIciRNA). Due to lacking the 3' and 5' ends, circRNAs were long considered non-coding RNAs. However, recent studies have revealed that many circRNAs were translated to proteins or peptides through internal ribosomal entry site (IRES), N6-methyladenosine (m6A) elements, A-to-I RNA editing, exon junction complex (EJC)-mediated initiation, ribosome shunting, and repeat-associated non-AUG (RAN) translation. The proteins and peptides encoded by circRNAs play significant biological roles including competitively binding with the interaction proteins or signal molecules of their homologous proteins, directly interacting with their homologous proteins, and regulating signal transduction pathways. In this review, we introduced the translational mechanisms of circRNAs and summarized the associated pathways of proteins encoded by circRNAs in human common cancers, such as glioblastoma, colorectal cancer, triple negative breast cancer, gastric cancer, hepatocellular cancer, bladder cancer, etc.
    Keywords:  Cancer; Circular RNA; Internal ribosomal entry site; N6-methyladenosine; Translation
    DOI:  https://doi.org/10.1007/s12032-026-03306-6
  46. FEMS Yeast Res. 2026 Jan 05. pii: foag019. [Epub ahead of print]26
    The oxidative cost of losing low temperature viability protein 1 [Ltv1]: insights into cellular damage and homeostasis.
    McKayla Remines, Samuel A Ammerman, Jill B Keeney, Erin D Strome.
      The Ltv1 protein has been characterized with roles in ribosome biogenesis, maintenance of rRNA stability, ATP export, osmotic stress response, and signaling activation of the Target of Rapamycin pathway. We screened ltv1Δ/ltv1Δ mutants for additional phenotypic manifestations due to loss of Ltv1. We observed growth differences consistent with Ltv1's well characterized roles, alongside evidence supporting a less-established role in reactive oxygen species response. In further characterization of cells lacking Ltv1 we documented higher levels of endogenous ROS and a greater accumulation response of reactive oxygen species to exogenous stress. Utilizing RNA-Sequencing we then determined the gene expression differences underlying the ltv1-deficiency induced oxidative stress sensitivity. This work elucidates a new significant role of Ltv1 in cellular homeostasis and protection against damage.
    Keywords:   LTV1 ; RNA-sequencing; glutathione; oxidative stress; reactive oxygen species
    DOI:  https://doi.org/10.1093/femsyr/foag019
  47. Curr Opin Microbiol. 2026 Jun 20. pii: S1369-5274(26)00076-7. [Epub ahead of print]92 102782
    The diverse effects of stress in cross-feeding systems.
    Caleb A Hill, Aileen R Lee, William R Harcombe.
      Predicting how metabolically interdependent microbial communities will respond to stress is an important but difficult challenge. Synthetic microbial communities provide an important tool for identifying mechanisms that impact stress response in communities. In this review, we discuss the weakest-link hypothesis as a null model that predicts that all species in an interdependent community will be constrained by the species that is most sensitive to a given stress. The hypothesis is contingent on the assumptions that 1) stress does not alter metabolite exchange in a way that changes growth constraints, 2) cross-feeding does not alter the ability of cells to withstand stress, and 3) the amount of stress experienced by a species is not altered by partners through mechanisms unrelated to cross-feeding. We then present cases that violate these assumptions to highlight the complexity of ecological factors involved in community stress response. Finally, we discuss the evolutionary dynamics of cross-feeding microbial systems when exposed to stress and some important challenges for connecting work from synthetic communities to more complex systems.
    DOI:  https://doi.org/10.1016/j.mib.2026.102782
  48. Nat Commun. 2026 Jun 23.
    Neuron type-specific translatomes in dorsal hippocampus during early memory consolidation.
    Mauricio M Oliveira, Olivia Mosto, Robert Carney, Wendy J Liu, Maggie Mamcarz, Emmanuel Makinde, Emily H Lu, Karen S A Ruiz, Carson C Schultz, Catherine Leckie, Thomas J Carew, Eric Klann.
      Long-term memory consolidation is a dynamic process that requires a heterogeneous ensemble of neurons, each with a specialized molecular signature. Considerable effort is devoted to identifying molecular changes associated with consolidation, but mostly hours or days after training, when it is already complete. Studies have shown that protein synthesis is elevated during the early stages of consolidation, but the impacted neuronal functions remain unclear. We hypothesize that mRNAs translated during early consolidation provide information on how diverse neurons involved in memory formation restructure their molecular signatures to support memory. We generate a landscape of the translatome of three neuron types in the dorsal hippocampus within the first hour of consolidation. Our results reveal unique translation programs among neurons, explained by features hard-coded in the mRNA. In this work, we uncover mechanisms controlling activity-induced translation in neurons and provide a new resource for scientists studying memory formation in health and disease.
    DOI:  https://doi.org/10.1038/s41467-026-74455-5
  49. J Fungi (Basel). 2026 Jun 07. pii: 414. [Epub ahead of print]12(6):
    Heat Shock Proteins in Medically Relevant Fungal Pathogens: From Molecular Chaperones to Virulence Factors and Therapeutic Targets.
    Leonardo Padró-Villegas, Héctor M Mora-Montes.
      Heat shock proteins (HSPs) are highly conserved molecular chaperones that play a key role in maintaining protein homeostasis and cellular survival under stress conditions. Clinically relevant human pathogenic fungi include opportunistic fungi, dimorphic fungi, dermatophytes, Mucorales, and other pathogenic groups. HSPs, including Hsp90, Hsp70, Hsp60, Hsp40, and Hsp110, are essential for the correct nascent protein folding, aggregation prevention, and degradation of misfolded polypeptides. Fungal pathogens frequently encounter environmental and host-imposed stresses, including oxidative stress, temperature fluctuations, and antifungal treatments. This review synthesizes and critically analyzes current evidence on the role of HSP families in essential processes linked to fungal virulence, including morphogenetic transitions, biofilm formation, maintenance of cell wall integrity, and interactions with host immune cells. Beyond their canonical chaperone functions, HSPs act as central mediators in pathogenic processes, such as morphogenesis transitions, biofilm formation, cell wall integrity, and interactions with host immune cells. Hsp90 stabilizes key signaling proteins involved in stress responses, morphogenesis, and antifungal resistance, while Hsp60 and Hsp70 contribute to mitochondrial function, cell wall integrity, and immune modulation. Disruption of these chaperones impairs growth, reduces virulence, and increases susceptibility to antifungal agents. The rise of antifungal resistance underscores the urgent need for new therapeutic strategies. Targeting fungal HSPs has emerged as a promising approach due to their essential roles in stress tolerance and pathogenesis. Hsp90 inhibitors, including geldanamycin derivatives and other small molecules, have demonstrated the ability to impair fungal growth, reduce virulence traits, and sensitize resistant strains to conventional antifungal drugs. Combining HSP inhibitors with existing antifungal drugs represents a potential strategy to overcome resistance and improve treatment outcomes. This review summarizes the current knowledge on HSPs in pathogenic fungi, focusing on their roles in stress adaptation, virulence, host-pathogen interaction, antifungal resistance, and their potential as targets for novel antifungal therapies.
    Keywords:  antifungal resistance; cell adhesion; chaperones; fungal infections; thermotolerance; virulence factors
    DOI:  https://doi.org/10.3390/jof12060414
  50. Proc Natl Acad Sci U S A. 2026 Jun 30. 123(26): e2604695123
    p53 overrides METTL5 loss-induced tumor suppression via mitochondrial respiration.
    Guozhi Li, Qiujie Li, Jun Zhang, Yifei Huang, Wenjun Tao, Yali Cheng, Jiaju Sun, Jingying Yuan, Rui Zhang, Xiao-Min Liu, Jun Zhou.
      The tumor suppressor p53 is pivotal in repressing tumorigenesis under physiological conditions. Paradoxically, we find that wild-type (WT) p53 plays an oncogenic role in relieving METTL5 depletion-caused cancer regression by sustaining mitochondrial respiration. The methyltransferase METTL5 is upregulated in non-small cell lung cancer (NSCLC) and associated with advanced tumor grade and poor prognosis. Depletion of METTL5 impairs NSCLC cell proliferation and migration in vitro and in vivo, with p53-null cells displaying enhanced sensitivity. While METTL5-depletion inhibits cytoplasmic translation in both p53-WT and p53-null cells, only cells lacking p53 exhibit severe tumor regression due to defective mitochondrial protein synthesis and consequent respiratory dysfunction. Mechanistically, p53 binds 5'UTR of TOMM40, the crucial gatekeeper of mitochondrial protein import, to enforce its exclusion from translation. METTL5 loss promotes p53 nuclear retention via inhibiting MDM2-mediated p53 ubiquitination, alleviating its translational suppression of TOMM40, and supporting oxidative phosphorylation. Remarkably, the combination targeting of p53 and METTL5 synergistically attenuates the proliferation and migration in p53-WT cancer cells. Our study elucidates the essential role of p53 in supporting tumor viability upon METTL5 deficiency by maintaining mitochondrial respiration. Meanwhile, it provides a molecular foundation for developing therapeutic strategies regarding cancers with WT p53.
    Keywords:  METTL5; lung cancer; mitochondrial respiration; p53; protein synthesis
    DOI:  https://doi.org/10.1073/pnas.2604695123
  51. Int J Mol Sci. 2026 Jun 20. pii: 5593. [Epub ahead of print]27(12):
    RNA-Binding Protein Occupancy Composition Predicts Long Noncoding RNA Subcellular Localization.
    Hidenori Tani.
      The subcellular localization of long noncoding RNAs (lncRNAs) is a central determinant of their function, yet its molecular determinants remain incompletely defined, and most existing predictors rely on the primary sequence. Because RNA-binding proteins (RBPs) are the proximal effectors of RNA compartmentalization, this study tested whether the composition of RBPs bound to a lncRNA is predictive of its nuclear or cytoplasmic localization. Enhanced crosslinking and immunoprecipitation (eCLIP) occupancy for 139 RBPs in K562 cells was integrated with the cytoplasmic-nuclear relative concentration indices (CN-RCIs) derived from matched subcellular fractionation, and localization was modeled under chromosome-grouped cross-validation with nested regularization. RBP-occupancy composition predicted localization beyond the transcript size and total binding amount (incremental cross-validated coefficient of determination, delta-R-squared = 0.17; receiver-operating-characteristic area under the curve, AUC = 0.73, a moderate-strength association; Freedman-Lane permutation, p = 0.005). This increment persisted (delta-R-squared = 0.12; p = 0.005) against an expanded baseline that additionally absorbed the transcript abundance, intron content and exon number, indicating predictive information that is not reducible to these transcript features, and the classifier was well calibrated (Brier score = 0.10; expected calibration error = 0.02). The signed coefficient profile separated RBP function systematically: factors acting in nuclear processes (splicing, 3'-end processing, and nuclear-matrix association) carried negative, nuclear-direction weights, whereas factors acting in cytoplasmic processes (translation and messenger RNA stability) carried positive, cytoplasmic-direction weights (Mann-Whitney p = 0.013). The profile generalized across cell lines: a K562-trained model predicted HepG2 localization (transfer AUC = 0.71 using 76 shared RBPs), and HepG2 reproduced the association independently (AUC = 0.77). The association is correlational and of moderate strength; it is presented as an interpretable, RBP-occupancy-based complement to sequence-based predictors of lncRNA localization.
    Keywords:  RNA-binding protein; cross-validated prediction; eCLIP; long noncoding RNA; nuclear retention; subcellular localization
    DOI:  https://doi.org/10.3390/ijms27125593
  52. Life Sci Alliance. 2026 Sep;pii: e202503592. [Epub ahead of print]9(9):
    Conserved HSP60 structure with lineage- and context-specific regulation in cnidarians.
    Saborni Chowdhury, Avery J Kruger, Liza M Roger.
      Heat shock proteins safeguard proteostasis under stress. We examined mitochondrial chaperonin HSP60 in three cnidarians to assess stress responses. We evaluated HSP60 expression in Pocillopora acuta (hard coral), Exaiptasia diaphana (sea anemone), and Cassiopea xamachana (upside-down jellyfish) using immunoblotting. In P. acuta, HSP60 was not detected at the fragment level under either control (25°C) or heat-stress (30°C). In contrast, isolated cells showed transient HSP60 expression under both temperature conditions, indicating context-dependent regulation in coral. E. diaphana and C. xamachana showed elevated HSP60 expression over 24 h when stressed (+5°C above laboratory optima). These patterns indicate lineage-specific regulatory mechanisms underlying chaperone-mediated stress response pathways. Thus, thermal sensitivity varies among species and across biological contexts. Consistent antibody cross-reactivity prompted evolutionary analysis. Phylogenetic analyses confirmed cnidarian HSP60 proteins are orthologous to vertebrate HSP60, demonstrating deep conservation across Metazoa. Although HSP60 is ancient and highly conserved, its role in regulating mitochondrial proteostasis varies across early-diverging metazoans. This study underlines the role of chaperone plasticity in cnidarian thermotolerance and diverging bleaching susceptibility of symbiotic cnidarians.
    DOI:  https://doi.org/10.26508/lsa.202503592
  53. Int J Mol Sci. 2026 Jun 09. pii: 5228. [Epub ahead of print]27(12):
    N7-Methylguanosine Modification in Colorectal Cancer: Molecular Insights and Clinical Implications.
    Qin Zhang, Chunchun Li, Yonglan Zhu, Meirong Yu, Yanshan Liu, Yuqiong Xie, Jiang Cao.
      Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, characterized by a multi-step carcinogenesis process involving genetic mutations and epigenetic alterations. Despite advances in screening and therapy, challenges such as treatment resistance, recurrence, and metastasis persist. Emerging evidence highlights the critical role of epigenetic modifications, particularly N7-methylguanosine (m7G), in post-transcriptional regulation. This ubiquitous RNA modification participates extensively in tumor biological behaviors by regulating RNA stability, processing, and translation. Studies have shown that dysregulation of m7G modification is closely associated with adverse clinical outcomes in CRC. This review systematically summarizes the biological functions of m7G modification and its key regulatory proteins (such as METTL1/WDR4, eIF4E, etc.), with a focus on their roles in the pathogenesis, progression, prognosis, and diagnosis of, as well as therapy for, colorectal cancer. m7G modification and related molecules hold potential as novel biomarkers and therapeutic targets, thereby providing new strategies for the precision diagnosis and treatment of colorectal cancer.
    Keywords:  METTL1; N7-methylguanosine; colorectal cancer; eIF4E; epigenetic modification
    DOI:  https://doi.org/10.3390/ijms27125228
  54. Mol Biol Evol. 2026 Jun 23. pii: msag153. [Epub ahead of print]
    The transcriptional and translational outcomes for pseudogenes in bacterial endosymbionts.
    Arkadiy Garber, Justus Nwachukwu, Ryan Stikeleather, Courtney York, John P McCutcheon.
      Intracellular bacteria in the early stages of host adaptation often show extraordinarily disrupted genomes, where up to half of their ancestral genes are found in a pseudogenized state. The mealybug Pseudococcus longispinus hosts two bacterial endosymbionts with high pseudogene loads, Symbiopectobacterium endolongispinus and Sodalis endolongispinus. Here, we measure transcript abundance, ribosome-associated RNA, and protein abundance in these bacterial symbionts to understand how bacteria avoid (or fail to avoid) accumulating large amounts of non-functional RNAs and proteins from these pseudogenes. Consistent with previous work, we show that pseudogene transcripts remain detectable, but at lower levels compared to those from intact and functional genes, and that relatively few pseudogenes yield detectable proteins in proteomic data. However, we find that many pseudogene transcripts still bind to Symbiopectobacterium ribosomes, and uncover a possible role for the tmRNA ribosome rescue system in the targeting of pseudogene proteins for degradation. Our results suggest a possible mechanism by which bacterial endosymbionts remove aberrant pseudogene-derived proteins during the critical time when many pseudogenes have formed but not enough time has passed for sequence evolution to erode ribosome binding sites from pseudogene transcripts.
    Keywords:  mealybug; proteomics; pseudogene; ribosome profiling; ribosome rescue; tmRNA; transcription; translation
    DOI:  https://doi.org/10.1093/molbev/msag153
  55. J Bacteriol. 2026 Jun 22. e0007626
    Activation of the antibiotic resistance factor WhiB7 can stimulate aggregate biofilm formation in stationary phase Mycobacterium smegmatis by reinitiating translation.
    Mitchell D Meyer, Megan Bergkessel, William H DePas.
      There is a growing understanding that slow growth and dormancy due to nutrient deprivation are very common physiological states exhibited by bacterial communities in a myriad of environments. However, very little is known about the role of slow growth and dormancy in biofilm regulation. Here, we utilize tractable dormancy and aggregation assays in nontuberculous mycobacteria (NTM) to ask the fundamental question of how growth arrest impacts the processes of aggregation and dispersal. First, we show that the well-conserved dormancy regulator DosSR affects biofilm formation in Mycobacterium smegmatis, as a dosR deletion mutant undergoes spurious re-aggregation and dispersal during aerobic late stationary phase. Identification of a suppressor mutation blocking re-aggregation in the ΔdosR mutant allowed us to determine a role for the antibiotic resistance factor WhiB7 in driving re-aggregation in M. smegmatis. We utilized BioOrthogonal NonCanonical Amino acid Tagging (BONCAT), qPCR, and quantitative aggregation assays to build a model wherein reductive stress in ΔdosR potentiates stationary phase translation in a WhiB7-dependent manner, permitting aggregation in dormant stationary phase cells. In addition, during stationary phase, WhiB7-activating reducing agents and antibiotics could trigger re-aggregation in both wild-type M. smegmatis and clinical isolates of the opportunistic NTM pathogen Mycobacterium abscessus. Finally, we determined that, in contrast to aerobic stationary phase, M. smegmatis does not aggregate or disperse in response to chemical cues or antibiotics under the Wayne model of hypoxic dormancy. Our work reveals a regulatory interaction between dormancy and aggregation that could have broad implications for treating and preventing NTM biofilms.IMPORTANCEMycobacteria aggregate to form multicellular biofilms that provide protection from external stressors and increase antibiotic tolerance. Understanding the pathways regulating biofilm formation can aid the identification of useful targets for developing new drugs. With a growing appreciation that pathogens are often in a slow growth/dormant state during infection, we investigate how dormancy affects biofilm formation and dispersal in two nontuberculous mycobacteria (NTM) species: Mycobacterium smegmatis and the opportunistic pathogen Mycobacterium abscessus. We find that activation of the WhiB7-mediated antibiotic response permits biofilm formation in aerobic stationary phase by reinitiating protein synthesis; however, cells under hypoxic dormancy are unresponsive. Our work provides important context to combatting biofilm formation in infection sites, informing future studies and aiding design of biofilm dispersal agents.
    Keywords:  NTM; antibiotic tolerance; biofilms; dormancy; two-component systems
    DOI:  https://doi.org/10.1128/jb.00076-26
  56. Int J Mol Sci. 2026 Jun 11. pii: 5310. [Epub ahead of print]27(12):
    PKCβII Activation Promotes Membrane-Proximal Enrichment of Ribosome-Bound RACK1.
    Ekaterina Shuvalova, Polina Fortygina, Gulnur Smirnova, Natialia Bal, Elena Alkalaeva, Peter Kolosov.
      The scaffold protein RACK1 (Receptor for Activated C Kinase 1) integrates signaling and translation, acting as a core component of the 40S ribosomal subunit. It binds activated Protein Kinase C (PKC) isoforms and membrane receptors. We used an auxin-inducible degron (AID2) system in human HAP1 cells to selectively deplete the free (cytoplasmic) pool of RACK1. The engineered RACK1-mAID-mClover3 fusion was rapidly degraded in the cytoplasm upon addition of 5-phenyl-indole-3-acetic acid (5-Ph-IAA), while the ribosome-bound pool remained detectable in ribosomal fractions, indicating that ribosome association makes RACK1 relatively less accessible to AID2-mediated proteolysis. Upon activation of PKCβII with phorbol-12-myristate-13-acetate (PMA), imaging at defined time points revealed closely matched kinetics of PKCβII membrane recruitment and membrane-proximal enrichment of ribosome-bound RACK1, peaking at ~10 min. Our data support a model in which activated PKCβII engages ribosome-bound RACK1 at membrane-proximal sites, consistent with a diffusion-capture mechanism in which PKCβII first accumulates at the membrane and then captures ribosome-bound RACK1, thereby recruiting the translational machinery to sites of signal input for membrane-proximal translation. These findings provide new insights into the spatial organization of translation.
    Keywords:  PKCβII; RACK1; local translation; ribosome
    DOI:  https://doi.org/10.3390/ijms27125310
  57. Annu Rev Cell Dev Biol. 2026 Jun 25.
    Hidden Messages in Extracellular Vesicles: Cross-Kingdom RNA Communication in Plant and Microbe Interactions.
    Qiang Cai, Simoné Murguia, Hailing Jin.
      RNAs are versatile polynucleotides that perform essential functions in coding, regulation, catalysis, and structural organization across all forms of life. While most RNAs function endogenously within an organism, certain RNAs, including small RNAs, messenger RNAs, long noncoding RNAs, and other RNA species, can cross organismal boundaries and regulate cellular processes in recipient organisms, a phenomenon termed "cross-kingdom" or "cross-species" RNA communication. These transferred RNAs play a pivotal role in regulating host-microbe interactions. Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that serve as vehicles for transporting RNAs and other cargoes from donor to recipient cells or organisms to regulate diverse cellular processes. This review summarizes recent advances in our understanding of EVs and their functions in shuttling regulatory molecules, especially RNAs, between hosts and microbes, between hosts and parasites or pests, and even between microbes. Elucidating these mechanisms will enable the development of innovative crop protection strategies.
    DOI:  https://doi.org/10.1146/annurev-cellbio-111524-091450
  58. Mater Today (Kidlington). 2025 Dec;91 124-147
    Engineering bone tissue with mRNA: from molecular design and delivery to clinical applications.
    Claudia Del Toro Runzer, Martijn van Griensven, Elizabeth Rosado Balmayor.
      Bone possesses an intrinsic ability to regenerate after injury, but this capacity is often compromised in pathological conditions. Non-healing fractures are typically treated with autografts, which involve additional surgeries, patient discomfort, and risk of complications. Alternative strategies, such as the administration of growth factor proteins or plasmid DNA, have shown promise but are limited by high costs, immunogenicity, and safety concerns. Recently, messenger RNA (mRNA) therapies have emerged as a compelling alternative for inducing bone regeneration. Unlike DNA, mRNA functions in the cytoplasm, eliminating the need for nuclear entry and minimizing the risk of insertional mutagenesis. It is also transiently expressed and fully degradable, offering a favorable safety profile. Chemical modifications to mRNA can improve its stability, translational efficiency, and reduce innate immune activation, making it a versatile and potent tool for therapeutic applications. In this review, we explore the types of chemical modifications used to enhance mRNA performance, the delivery strategies employed for efficient cellular uptake (including in vivo and ex vivo routes), and the design of biomaterial scaffolds that support bone repair while enabling spatial and temporal control of gene expression. We also discuss the translational potential of mRNA-based approaches, including safety considerations, manufacturing scalability, and cost-effectiveness. Collectively, these advances position chemically modified mRNA as a next-generation therapeutic for bone regeneration, with the potential to overcome the limitations of current treatments and improve outcomes for patients with challenging fractures.
    Keywords:  Bone regeneration; Chemically modified mRNA; Fractures; Gene delivery; Tissue engineering; Transcript therapy; mRNA therapeutics
    DOI:  https://doi.org/10.1016/j.mattod.2025.11.002
  59. Front Aging Neurosci. 2026 ;18 1809812
    N-terminal modifications as fate switches in neurodegeneration: a mechanistic review.
    Disha Mukherjee, Sampath Raghul Kannan, Ramasamy Tamizhselvi.
      The accumulation of aberrant proteins or their impaired clearance leads to neurodegenerative diseases (NDs). The protein amino terminus (Nt) and its modifications determine the fate of proteins and their cellular effects. Nt acetylation, Nt methylation, and Nt myristoylation are protein Nt modifications implicated in the pathogenesis of proteinopathies like Alzheimer's, Parkinson's, and Huntington's diseases by regulating the protein lifespan, folding, and interaction with protein/DNA. In particular, Nt acetylation shields proteins from degradation or targets them for the same, thereby affecting their fate. Distinct enzymes catalyze Nt acetylation, Nt methylation, and Nt myristoylation, and these modifications compete for the nascent polypeptide at the ribosomal exit tunnel. Dysregulation of Nt modifications initiates the protein aggregation cascade and could potentially induce neuroinflammation and neurodegeneration. Here, we review Nt modifications and their emerging roles in the pathogenesis of NDs. Further, we highlight the crosstalk among distinct Nt modifications and explore how their convergence may shape disease vulnerability and progression.
    Keywords:  Alzheimer’s disease; N-terminal modifications; Nt acetylation; Nt methylation; post-translational modifications
    DOI:  https://doi.org/10.3389/fnagi.2026.1809812
  60. Trop Anim Health Prod. 2026 Jun 22. pii: 368. [Epub ahead of print]58(6):
    Relative abundance of genes regulating proliferation and apoptosis of corpus luteum during cold and hot seasons in Egyptian buffaloes.
    Samaa M Galal, Sally Ibrahim, Karima Mahmoud, Ola Adel, Aya A Shokry, M S El-Belely, S T Ismail.
      The worldwide climate is thought to be drastically changing as a result of the global temperatures, a phenomenon known as "global warming". Thermal stress is a crucial obstacle facing buffalo cyclicity. Investigation of the molecular regulation concerning proliferation and apoptosis of corpus luteum (CL) is not fully comprehended in buffaloes. We aimed to (1) study mRNA expression of candidate genes related to proliferation (PGR, AGTR1, and LHCGR) and apoptosis (TNFα, BAX, FASLG, CASP3, AGTR2 and PTGS2), (2) explore effect of thermal stress on the expression of HSP70, NOS1, NOS2 mRNAs, NO and SOD concentrations in CL homogenate during different stages of CL. For this, ovaries (n = 70) were collected in pairs from buffaloes during cold and hot seasons. According to morphology of CL, samples were divided into: early, mid, and late. For RNA isolation, NO and SOD concentrations, small sections from CL stages were frozen in - 80 °C. The results showed that PGR, AGTR2, TNFα, BAX, cALP2beta and PTGS2 mRNAs decreased (P < 0.001) at different stages of CL at hot season. The decline of AGTR2 associated with decreased NOS2 mRNA, which consequently affected TNFα, BAX, and CASP3 mRNAs. Apoptosis might be affected by direct effect of AGTR2 on CASP3 during thermal stress. We supposed that NO had a regulatory role during early and late stages of CL. It could be concluded that thermal stress (THI > 68) changed the expression of proliferation and apoptosis genes of CL in Egyptian buffaloes. Finally, the thermal stress in cold or hot seasons has marked impact on CL dynamics.
    Keywords:  Apoptosis; Buffaloes; Corpus luteum; Gene expression; Proliferation; Thermal stress
    DOI:  https://doi.org/10.1007/s11250-026-05120-8
  61. Neurol Int. 2026 Jun 07. pii: 112. [Epub ahead of print]18(6):
    RNA-Binding Proteins in Ageing and Age-Related Disease.
    João Miguel Alves Ferreira, Sergii Tukaiev, Vaitsa Giannouli.
      RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid-liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed.
    Keywords:  RNA-binding proteins; TDP-43; ageing; alternative splicing; cellular senescence; neurodegeneration; post-transcriptional regulation
    DOI:  https://doi.org/10.3390/neurolint18060112
  62. Brain. 2026 Jun 25. pii: awag222. [Epub ahead of print]
    STMN2 protein depletion via translation deficits and stress granules in amyotrophic lateral sclerosis.
    Brittany C S Ellis, Anna Sanchez Avila, Wan-Ping Huang, Sabin J John, Sam Bonsall, Rachel E Hodgson, Vedanth Kumar, Matthew Nolan, Ryan J H West, Susan G Campbell, Kurt J De Vos, Clotilde Lagier-Tourenne, J Robin Highley, Johnathan Cooper-Knock, Tatyana A Shelkovnikova.
      STMN2 is an abundant neurospecific protein dysregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We previously reported that cellular stress can lead to STMN2 loss due to TDP-43 nuclear condensation. Here, using human and murine neuronal cell models, multiple pharmacological tools, in situ single-molecule analysis of translation and RNA localisation, and longitudinal analysis of neuronal fitness/survival, we establish TDP-43-independent mechanisms of STMN2 depletion under stress. We find that human STMN2 protein level is extremely labile under acute high-magnitude stress. Early in stress, STMN2 is suppressed via activated proteasomal degradation, phosphorylation and translation repression by stress granules, independently of TDP-43 loss of function in splicing. We further show that STMN2 protein level is highly sensitive to chronic translation deficits, such as those elicited by prolonged low-grade stress. We find that low pre-stress STMN2 sensitises neuronal cells to stress-induced apoptosis, whereas moderately increased STMN2 is protective under stress. Finally, we demonstrate that STMN2 mRNA is upregulated in non-TDP ALS (ALS-FUS) models, which may compensate for translation/stress granule defects in this disease subtype. Consistent with the compensation hypothesis, STMN2 mRNA is also upregulated in the relatively spared (cortex), but not severely affected (spinal cord), CNS regions in ALS-TDP. In conclusion, our study implicates two common denominators in neurodegeneration - dysregulation of translation and stress granules - in STMN2 depletion, independent of TDP-43 loss of function. It also describes an RNA-based compensatory mechanism in ALS underling the unique vulnerability of neurons with developing TDP-43 pathology.
    Keywords:  ALS; FUS; STMN2; TDP-43; protein translation; stress granule
    DOI:  https://doi.org/10.1093/brain/awag222
  63. Talanta. 2026 Jun 21. pii: S0039-9140(26)00836-2. [Epub ahead of print]310 130180
    Immunoelectroanalytical multiplexing of RNA methylation signatures to decode oncogenic point mutations in cancer cells.
    Víctor Pérez-Ginés, Rebeca M Torrente-Rodríguez, Raquel Rejas-González, Ana Montero-Calle, María Pedrero, José M Pingarrón, Rodrigo Barderas, Susana Campuzano.
      Epigenomic and epitranscriptomic alterations-particularly RNA methylations such as N6-methyladenosine (m6A), N5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G)-are increasingly recognized as pivotal regulators in the pathobiology of colorectal cancer (CRC) and other highly prevalent disorders. Despite their growing clinical and biological relevance, rapid and robust electrochemical strategies enabling the single (m1A, m7G) or multiplexed quantification of these RNA modifications remain unavailable. Herein, we report an indirect competitive, four-analyte amperometric immunoassay that enables the simultaneous determination of m6A, m5C, m1A, and m7G. BSA-conjugated methylated synthetic nucleotides covalently attached to magnetic carboxylated microsized-beads (HOOC-MμBs) competed with freely methylated nucleotides in the target sample for specific anti-epimark detection antibodies. Thereafter, labeling with horseradish peroxidase (HRP)-conjugated secondary antibodies (Ab2-HRP) enabled amperometric readout at screen-printed carbon electrodes (SPCEs) for single or multiplexed transduction. The developed bioplatforms exhibited high selectivity, negligible cross-interference, and a significantly reduced assay time (30 min), supporting their integration into a robust multiplexed format. Application in CRC cellular scenarios, using only nanograms of total RNA, allowed differential profiling of basal and pathway-activated states across five cell lines, revealing distinct RNA methylation patterns associated with diverse biological and genetic backgrounds. Moreover, as proof of concept, an octuple-detection configuration was implemented for parallel analysis of the four methylations in two cell types, wild-type and harboring the clinically relevant KRAS G12V mutation, allowing the evaluation of associations between the target epimark expression levels and this oncogenic point mutation.
    Keywords:  Cancer cells; Multiplexed amperometric bioplatform; Point mutations; RNA methylation
    DOI:  https://doi.org/10.1016/j.talanta.2026.130180
  64. PLoS One. 2026 ;21(6): e0342288
    Enhanced IGFL1 translation in response to IL-1β is controlled by distinct 3'UTR elements.
    Giulia Cardamone, Melanie Flohr, Rebecca Raue, Irina Bode, Sofie P Meyer, Sven Hauns, Rolf Backofen, Tobias Schmid.
      Translation is a crucial regulatory mechanism involved in several diseases, including cancer, where pro-inflammatory conditions within the microenvironment have been shown to modulate the translation of specific mRNAs. In the present study, we focused on the regulation of insulin growth factor-like family member 1 (IGFL1) in MCF7 breast cancer cells in response to pro-inflammatory IL-1β and observed an induction of both transcription and translation. We characterized the 3' untranslated region as regulatory hub for the post-transcriptional regulation and identified a distinct G-rich region to confer the IL-1β-dependent translational increase. Our study therefore provides new insights into the translation regulation of IGFL1 in the context of an inflammatory tumor microenvironment.
    DOI:  https://doi.org/10.1371/journal.pone.0342288
  65. Nucleic Acids Res. 2026 Jun 22. pii: gkag594. [Epub ahead of print]54(12):
    RNA G-quadruplexes function as a tunable switch of FUS phase separation.
    Jenny L Carey, Miyuki Hayashi, Emily Welebob, Laura R Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A DePierro, Zheng Shi, James Shorter, Sua Myong, Aaron Haeusler, Lin Guo.
      Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. Although short rG4s interact with both soluble and condensed FUS, they preferentially engage the soluble pool, likely shifting the equilibrium toward dispersion. Leveraging these mechanistic insights, we developed a bioinformatic pipeline that uncovered more rG4 inhibitors that robustly reverse FUS LLPS and aggregation. Our findings establish rG4s as chemically programmable regulators of protein phase behavior and provide a blueprint for engineering RNA-based therapeutics that dissolve pathogenic FUS assemblies. More broadly, this work directly links RNA secondary structure to distinct functional outcomes in phase behavior, establishing a structure-function paradigm for RNA control of condensates, demonstrating implications in both fundamental biology and therapeutic development.
    DOI:  https://doi.org/10.1093/nar/gkag594
  66. BMC Plant Biol. 2026 Jun 24.
    Genes associated with translation and oxidative phosphorylation as components of the translational response in nodulated and water-restricted soybean.
    Mauro Martínez-Moré, Carla V Filippi, Guillermo Eastman, Gastón Quero, Mariana Sotelo-Silveira, Selene Píriz-Pezzutto, José Sotelo-Silveira, Omar Borsani, María Martha Sainz.
       BACKGROUND: Soybean primarily acquires nitrogen through symbiosis with nitrogen-fixing bacteria. Water deficit (WD) is a major stress limiting crop yield. Nodulation may enhance drought tolerance in legumes by modulating nitrogen and hormone metabolism, osmotic adjustment, and antioxidant defenses; however, the molecular basis underlying the differential WD responses between N-fix and N-fed plants remain unclear. Translational control of gene expression is a key regulatory mechanism during stress.
    RESULTS: We compared the transcriptome and translatome of soybean roots from N-fix and N-fed plants exposed to WD across four combined treatments. N-fix plants under WD exhibited more complex responses in terms of total differentially expressed genes (DEGs) compared to N-fed plants. This increased complexity was also evident among translationally regulated DEGs and differentially expressed transcription factors, whose involvement in WD responses of N-fix plants is novel. Co-expression network analysis identified modules associated with core biological processes encompassing nodulation, WD, and notably, their interplay was particularly prominent in Module 1, which was enriched in genes related to ribosomal protein synthesis and oxidative phosphorylation (OXPHOS). Guilt-by-Association analysis enabled the prediction of novel functions for differentially expressed, uncharacterized hub genes related to stress and/or nodulation responses.
    CONCLUSIONS: Translational regulation of genes involved in OXPHOS and translation initiation emerged as a central response in N-fix plants under WD. These findings reveal distinct molecular adaptations in N-fix soybean roots facing WD and highlight translational control as a key regulatory layer. We also identified promising candidate genes-including transcription factors and uncharacterized hub genes under translational regulation-that represent potential targets for improving drought tolerance in legumes once validated functionally.
    Keywords:  Drought tolerance; Oxidative phosphorylation; Root metabolism; Soybean; Symbiotic nitrogen fixation; Translation; Translational control
    DOI:  https://doi.org/10.1186/s12870-026-09344-6
  67. Plant Cell. 2026 Jun 25. pii: koag196. [Epub ahead of print]
    The mRNA covalent modification dihydrouridine regulates transcript turnover and photosynthetic capacity during plant abiotic stress.
    Li'ang Yu, Giovanni Melandri, Anna C Nelson Dittrich, Sebastian Calleja, Diep R Ganguly, Kyle Palos, Emily K Brewer, Hillary Fischer, Bruno Rozzi, Aparna Srinivasan, Toshihiro Obata, Hamada AbdElgawad, Gerrit T S Beemster, Riley Henderson, Ciara Garcia, Xiaodan Zhang, David Stern, Andrea Eveland, Eric Lyons, A Elizabeth Arnold, Aleksandra Skirycz, Susan J Schroeder, Brian D Gregory, Duke Pauli, Andrew D L Nelson.
      RNA covalent modifications (RCMs) influence RNA stability and translation efficiency, and thus play critical roles in eukaryotic growth and development. However, their role in regulating plant performance under abiotic stress remains largely unexplored. Here, we integrated multi-omics data in six Sorghum bicolor accessions under water-limiting conditions in the field to explore the relationship between RCMs and drought response. Within a stress and photosynthesis-associated gene co-expression module, we identified SbDUS2, a member of a family of enzymes conserved across eukaryotes, that catalyzes the reduction of uracil to dihydrouridine (DHU) on RNA molecules. DHU-modified transcripts in this module were enriched for photosynthetic functions and showed strong correlation with photosynthetic traits. To elucidate the function of this RCM, we characterized loss of function dus2 mutants in Arabidopsis thaliana. Under control conditions, these DHU-deficient mutants exhibited impaired germination and delayed development. Furthermore, under heat or water-limiting conditions, these mutants showed significantly reduced net CO2 assimilation and survival. Using multiple transcriptome-wide RNA stability assays, we demonstrated that transcripts associated with lower DHU levels in a dus2 background generally exhibited increased stability compared to Col-0 controls. Particularly, lack of DUS2 led to the hyperstability of photosynthesis-related transcripts, impeding their turnover and likely preventing proper photosynthetic acclimation during stress. We propose a model where DHU acts as a critical post-transcriptional regulator marking mRNAs for rapid turnover under stress, highlighting an overlooked regulatory layer contributing to plant resilience.
    Keywords:  Abiotic stress response; Epitranscriptome; Photosynthesis; RNA modification; Systems biology; mRNA dihydrouridylation
    DOI:  https://doi.org/10.1093/plcell/koag196
  68. Cell Signal. 2026 Jun 25. pii: S0898-6568(26)00350-5. [Epub ahead of print] 112695
    β-TrCP targets nucleolin and modulates phase separation to restrict ribosome biogenesis in myocardial infarction hearts.
    Junchu Tu, Huiling Zhang, Tonggan Lu, Anqi Zhou, Yu Zhang, Ao Li, Bin Liu, Xi-Yong Yu, Yan Xu, Yangxin Li.
      Myocardial infarction (MI) remains a significant global health challenge, as limited long-term efficacy of coronary interventions is largely due to inadequate cardiomyocyte (CM) regeneration. Ribosome biogenesis, a key driver of cell regeneration, and Nucleolin (NCL), a cardioprotective protein, have emerged as crucial factors in post-MI recovery. While liquid-liquid phase separation (LLPS) plays a dynamic role in cellular regulation, its impact on NCL-mediated ribosome biogenesis following MI remains unclear. Using Ribo-Halo, Ribo-disome, and AgNOR staining to map ribosome biogenesis, along with co-immunoprecipitation, molecular docking, FRAP, and confocal imaging to examine NCL ubiquitination and LLPS dynamics, we investigated these mechanisms. In MI mice and hypoxic cells, we identified an inverse correlation between the E3 ubiquitin ligase β-TrCP and NCL levels. Our Co-IP results demonstrate a functional interaction between β-TrCP and NCL in cytoplasm, and hypoxia induced LLPS transition of NCL in nuclear. NCL depletion impaired ribosome biogenesis and CM renewal. Our findings reveal NCL depletion-mediated by β-TrCP and LLPS formation as a key mechanism hindering cardiac repair post-MI. This study provides valuable insights and introduces potential therapeutic target for treating MI.
    Keywords:  E3 ubiquitin ligase; LLPS; Myocardial infarction; Nucleolin; Ribosome biogenesis
    DOI:  https://doi.org/10.1016/j.cellsig.2026.112695
  69. Int J Mol Sci. 2026 Jun 20. pii: 5586. [Epub ahead of print]27(12):
    The Research Progress in Targeted Therapy for Hypertension via Heat Shock Proteins.
    Bowen Sun, Yiming Jiao, Lin Lin, Xinhai Cui, Chao Li, Yunlun Li.
      As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies.
    Keywords:  heat shock proteins; hypertension; mechanism; targeted therapy
    DOI:  https://doi.org/10.3390/ijms27125586
  70. Neuroscience. 2026 Jun 21. pii: S0306-4522(26)00416-1. [Epub ahead of print]
    Establishment and validation of the NEX-RiboTag system for profiling the excitatory neuronal translatome in the postnatal mouse forebrain.
    Kangnan Zheng, Mengna Liu, Bingxue Jin, Guoliang Chai, Shanshan Wang, Yuanqing Yang, Ke Li, Huirong Huang, Changqing Lu, Xiannian Zhang, Jue Wang, Chen Zhang.
      Excitatory neurons are the principal neurons of the mammalian cortex and hippocampus and are essential for postnatal circuit maturation. Although single-cell RNA sequencing has refined their molecular taxonomy, dissociation-induced stress artifacts and the disconnect between transcript abundance and translational output can limit functional interpretation. Bulk proteomics lacks cell-type specificity, while single-cell proteomics remains constrained by limited sensitivity and throughput. These limitations leave a gap between transcriptional identity and cell-type-resolved translational output. Because translation directly governs the selective recruitment of mRNAs for protein synthesis, defining excitatory neuron-specific translatome in vivo is valuable to bridge this gap. Here, we established and validated a NEX-RiboTag mouse line for targeted profiling of ribosome-associated mRNAs in cortical and hippocampal excitatory neurons. By crossing Neurod6 (NEX)-Cre mice with RiboTag reporter mice, we achieved Cre-dependent ribosomal tagging in excitatory neurons of the cortex and the hippocampus. RNA sequencing analysis at the 1-week postnatal stage demonstrated enrichment of excitatory neuronal markers and depletion of inhibitory neuronal and glial transcripts. Comparative analysis revealed a clear separation between the whole-tissue transcriptome and the ribosome-associated fractions, with enrichment of synaptic and metabolic pathways characteristic of excitatory neurons. Together, these datasets provide a valuable resource for investigating translational regulation in postnatal excitatory neurons and for studying molecular programs underlying neuronal maturation and synapse formation.
    Keywords:  Excitatory neuron; NEX-Cre; RiboTag; Translatome
    DOI:  https://doi.org/10.1016/j.neuroscience.2026.06.027
  71. Front Immunol. 2026 ;17 1845134
    RNA modifications shape innate immunity and cellular adaptation during bacterial respiratory infection.
    Martina M Ivanova, Petya A Dimitrova, Milena N Leseva.
      Gram-negative bacteria are clinically significant pathogens responsible for life-threatening infections, including respiratory infections. These can be acute or persistent and can exacerbate existing chronic diseases, such as cystic fibrosis, COPD and lung cancer. In this review, we use Pseudomonas aeruginosa as a model organism that demonstrates the molecular complexity of host-pathogen interactions during lower airway infection. Specifically, we focus on RNA modifications and show that they, on the one hand, regulate bacterial fitness and pathogenicity, and on the other control the execution of an effective host innate immune response. Furthermore, we examine the role of epigenetic and epitranscriptomic modifications in the immune dysregulation observed in sepsis, with an emphasis on sepsis-induced lung injury. Innate immune memory - a cellular adaptation mechanism to primary microbial stimulation - results in training or tolerization of host cells towards secondary immune challenges. While fundamentally grounded in epigenetic and metabolic reprogramming, we propose that it can crosstalk with epitranscriptomic regulation. To overcome limitations imposed by animal models when investigating microbe-induced epitranscriptomic dynamics, we highlight physiologically-relevant in vitro tissue models that can complement work performed in vivo. Ultimately, a detailed understanding of the RNA modification landscape regulating host-pathogen interactions will help us identify new therapeutic targets and molecular pathways to better manage the clinical symptoms of bacterial respiratory infections and address the growing challenge of antimicrobial resistance.
    Keywords:  Pseudomonas aeruginosa; RNA modifications; epigenetic regulation; in vitro models; innate immune memory; innate immune response; lower airway infection
    DOI:  https://doi.org/10.3389/fimmu.2026.1845134
  72. Plant Commun. 2026 Jun 26. pii: S2590-3462(26)00285-3. [Epub ahead of print] 101977
    From activation to desensitization: How ABA balances plant growth and abiotic stress response?
    Wenguan Zhou, Yueni Fan, Weiqiang Li, Lam-Son Phan Tran, Kai Shu.
      Abscisic acid (ABA) is a central regulator of plant adaptation to abiotic stress, balancing stress responses with growth and development through the dynamic modulation of ABA signaling. Rapid activation of ABA signaling is essential for enhancing stress tolerance, whereas prolonged stress requires timely attenuation of the pathway to restore growth and prevent excessive defense responses. Recent studies have uncovered diverse mechanisms underlying ABA desensitization, including regulation by SnRK2 kinases, phytohormone crosstalk, nutrient signaling, protein trafficking, post-translational modifications, and feedback regulatory networks. Together, these interconnected mechanisms enable plants to fine-tune ABA signaling in response to developmental and environmental cues. In this review, we summarize recent advances in the molecular mechanisms that attenuate ABA signaling and rebalance growth and stress adaptation during prolonged stress. We also highlight questions and discuss strategies for engineering ABA signaling dynamics to improve crop resilience, productivity, and climate adaptation in increasingly variable environments.
    Keywords:  ABA desensitization; Abscisic acid (ABA); Plant growth and development; Protein modifications; SnRK2 kinases; Stress responses
    DOI:  https://doi.org/10.1016/j.xplc.2026.101977
  73. J Proteomics. 2026 Jun 24. pii: S1874-3919(26)00103-X. [Epub ahead of print] 105700
    Temporal proteomic analysis reveals a three-phase adaptation strategy in Phytophthora cinnamomi during salinity stress.
    Leann Seesom Vinson, Trevor Loo, Samarth Kulshreshtha, Renwick Charles Joseph Dobson, Claudia-Nicole Meisrimler.
      Phytophthora cinnamomi, a highly invasive hemibiotrophic oomycete, threatens global agriculture, forestry, and native ecosystems. Although drought and temperature effects on P. cinnamomi-host interactions are well studied, current knowledge of abiotic stress responses in P. cinnamomi remains largely centered on infection and phytopathology, with limited molecular insight into the pathogen's direct response to salinity independent of its host. To address this gap, we combined growth assays, time-resolved proteomics, and network analysis to define how P. cinnamomi responds and adapts to salinity exposure. Growth assays showed that NaCl-modified agar enhanced mycelial expansion in a concentration-dependent manner, with 100 mM NaCl significantly increasing growth at 48, 72, and 96 h compared with controls, while 50 mM NaCl remained comparable to control conditions. Temporal proteomic analysis of 100 mM NaCl treatment at 0, 1, 6, 12, and 24 h post treatment (HPT) revealed dynamic shifts in protein abundance. Early induction of ROS (Reactive Oxygen Species)-detoxifying enzymes, including glutathione S-transferases and peroxidases, was consistent with ROS-specific staining assays. Network analysis identified modules enriched for redox regulation, ATP generation, ion transport, and translational control, highlighting multi-layered adaptation to elevated NaCl levels. Notably, clusters of conserved hypothetical proteins were strongly upregulated, indicating unexplored stress tolerance components in Phytophthora species. Here, we propose that P. cinnamomi rapidly activates a three-phase strategy involving metabolism readjustments, redox defenses, and cellular structure alterations under salinity conditions. With increasing soil salinization due to climate change, our study provides first mechanistic insights into P. cinnamomi's adaptive plasticity and ecological resilience to abiotic stress. SIGNIFICANCE: This study represents the first, to our knowledge, temporal proteomic analysis of salinity stress adaptation in Phytophthora cinnamomi, revealing a sophisticated three-phase adaptation strategy. This research fundamentally advances our understanding of how this globally destructive plant pathogen, P. cinnamomi, maintains environmental resilience. Our discovery uses proteome remodeling which provides a framework for understanding stress tolerance in oomycetes, a group of microorganisms responsible for some of the world's most devastating agricultural and forest diseases. Our results show proteins involved in emergency damage control through metabolic recalibration to sustained adaptation. These findings have relevance for predicting pathogen behavior under climate change scenarios, where increasing soil salinity threatens agricultural productivity while simultaneously enhancing pathogen survival and virulence. By understanding how P. cinnamomi functions under prolonged salinity exposure, may provide insight for developing targeted biocontrol strategies and informs predictive models of disease pressure in salt-affected agricultural regions. The temporal analysis framework we present offers a broadly applicable approach for understanding microbial stress adaptation, with implications extending beyond plant pathology to environmental microbiology and biotechnology applications where stress tolerance is paramount.
    Keywords:  Abiotic stress; Oomycete; Oxidative stress; Phytophthora cinnamomi; Plant-pathogen; Proteomics
    DOI:  https://doi.org/10.1016/j.jprot.2026.105700
  74. Int J Nanomedicine. 2026 ;21 611081
    Size-Dependent Layered Double Hydroxide Nanoparticles Promote Osteogenesis and Bone Regeneration via METTL3-Dependent N6-Methyladenosine Modification of Runx2 mRNA.
    Yang Zhu, Weiwei Sun, Yaoyu Huang, Jianxin Li, Haozhe Jiang, Chao Luo, Fuyin Wan, Zhenyu Zhou.
       Background: The osteogenic efficacy of mesenchymal stem cell (MSC)-based bone regeneration is often limited by insufficient osteogenic differentiation. Layered double hydroxide (LDH) nanoparticles are promising biomaterials, but whether their intrinsic osteoinductive activity is regulated by particle size and epitranscriptomic mechanisms remains unclear. This study investigated whether LDH nanoparticles promote osteogenesis in bone marrow-derived MSCs (BMSCs) through METTL3-dependent N6-methyladenosine (m6A) modification.
    Methods: BMSCs were treated with 50 nm or 100 nm LDH nanoparticles under osteogenic induction. Osteogenic differentiation was evaluated by alkaline phosphatase activity, mineralization staining, osteogenic gene/protein expression, and cytoskeletal morphology. Global m6A levels and m6A regulator expression were assessed, and the role of METTL3 was examined using Mettl3 knockdown. Runx2 mRNA m6A enrichment and stability were analyzed by MeRIP-qPCR and actinomycin D chase assays. Bone regeneration was further evaluated using a GelMA-LDH hydrogel in a murine calvarial defect model.
    Results: LDH nanoparticles promoted BMSC osteogenesis in a size-dependent manner, with 100 nm LDH producing stronger ALP activity, mineralization, and osteogenic marker expression than 50 nm LDH. Mechanistically, 100 nm LDH increased global m6A methylation and selectively upregulated METTL3. Mettl3 knockdown markedly impaired osteogenesis and abolished the pro-osteogenic effects of LDH. LDH enhanced m6A modification of Runx2 mRNA and prolonged Runx2 transcript stability, thereby supporting RUNX2-mediated osteogenic programming. In vivo, GelMA-LDH implantation significantly enhanced calvarial bone repair and increased RUNX2 and METTL3 expression within defect regions.
    Conclusion: Among the two tested particle sizes, 100 nm LDH nanoparticles exhibited superior pro-osteogenic activity and promoted bone regeneration through a METTL3-dependent m6A mechanism that stabilizes Runx2 mRNA.
    Keywords:  METTL3; layered double hydroxide; m6A RNA methylation; osteogenic differentiation; size-dependent
    DOI:  https://doi.org/10.2147/IJN.S611081
  75. Microbiologyopen. 2026 Jun;15(3): e70356
    Synthetic Mirror Bacteria as a Frontier for Chiral Synthetic Biology and Biocontainment.
    Mohammad Nazrul Islam Bhuiyan.
      Chirality is a fundamental structural property of biological molecules that governs molecular recognition, enzymatic catalysis, and genetic information processing in living systems. Natural life exhibits a universal pattern of homochirality in which proteins are composed predominantly of l-amino acids, while nucleic acids contain d-sugars within their backbone structures. Advances in synthetic biology and chemical biology have stimulated growing interest in mirror biological systems that operate with inverted molecular chirality. In theory, mirror organisms would contain proteins composed of d-amino acids and nucleic acids built from l-sugars, forming a stereochemically inverted yet internally consistent biochemical framework that is largely incompatible with natural biological systems. This review examined the molecular foundations, engineering strategies, biosafety considerations, and ecological implications associated with the theoretical development of mirror bacteria. Particular emphasis is placed on the hierarchical organization of biological chirality and the stereochemical constraints that govern macromolecular folding, molecular recognition, and the processing of genetic information. Recent advances in the chemical synthesis of mirror proteins and mirror nucleic acids demonstrate that stereochemically inverted biomolecules can adopt stable structures and perform catalytic or informational functions. However, integrating these components into self replicating mirror cellular systems remains a major scientific challenge. Furthermore, the ecological interactions, evolutionary dynamics, and environmental persistence of mirror biological systems require careful biosafety evaluation and responsible governance. This review highlights key conceptual and technological challenges that must be addressed before mirror organisms can progress from theoretical constructs toward experimental feasibility.
    Keywords:  antimicrobial strategy; chiral medicine; mirror bacteria; mirror‐image antibiotics; prophylactic agents; synthetic biology
    DOI:  https://doi.org/10.1002/mbo3.70356
  76. Biomolecules. 2026 Jun 17. pii: 891. [Epub ahead of print]16(6):
    Molecular Equilibrist: The Small Heat Shock Protein IbpA from Mycoplasma.
    Innokentii E Vishnyakov, Alexey D Vedyaykin.
      Small heat shock proteins (sHSPs) serve as "first aid" stress-response proteins in both eukaryotes and prokaryotes. Their holdase activity enables binding to partially denatured proteins, maintaining them in a folding-competent state under stress. The sHSP IbpA from the mycoplasma Acholeplasma laidlawii is a unique member of its family, combining the functions of two Escherichia coli sHSPs that typically act in tandem. In this study, we demonstrate for the first time that IbpA forms distinct supramolecular structures under contrasting temperature stresses in crowded environments without any artificial truncations or mutations at the protein termini. Upon cooling, IbpA in vitro forms long fibril bundles, whereas heating induces the formation of large, rounded agglomerates. At the temperature optimal for culture growth, the protein exists as a mixture of short fibrils and small globules, with the latter predominating. IbpA's cellular localization mirrors in vitro properties, with an increased proportion of surface-associated proteins among the sHSP partners during cold shock. We also report, for the first time, a rapid and reversible transition of IbpA to a fibrillar form in response to cold. We propose hypotheses regarding potential roles of IbpA in the mycoplasma cell. IbpA from A. laidlawii appears to act as a "molecular equilibrist," protecting the cell against damage under opposing stresses, though the precise mechanism of its action during cold shock remains to be elucidated.
    Keywords:  cold shock; fibrils; globules; heat shock; mycoplasma; small heat shock proteins
    DOI:  https://doi.org/10.3390/biom16060891
  77. Int J Biol Sci. 2026 ;22(11): 5969-5987
    RNA variation as the driver of genomic efficiency and phenotypic complexity.
    Zhihua Jiang, Michee van Rooyen, Jennifer J Michal, Isyana Khaerunnisa, Saiful Anwar, Xing Fu, Jinzeng Yang, Steve P Miller.
      Despite decades of genome sequencing and annotation, a fundamental paradox remains unresolved: how organisms with finite and relatively stable gene numbers generate extraordinary phenotypic diversity. In this review, we propose that regulated RNA variant diversity provides a critical level of resolution for understanding genome expression, which we describe as a conceptual "minimal functional unit" for distinguishing distinct regulatory or functional outcomes. We synthesize evidence that transcript diversity arises through hierarchical and combinatorial RNA variation operating at three levels. At the genome level, diverse gene biotypes-including protein-coding genes, non-coding RNAs, pseudogenes, transposable elements, and bifunctional loci-expand regulatory capacity beyond classical gene definitions. At the gene level, alternative transcription initiation, splicing, and polyadenylation generate structurally and functionally distinct transcript isoforms. At the transcript level, RNA editing and chemical RNA modifications further modulate RNA stability, localization, translation, and immune recognition, forming a dynamic epitranscriptome. Together, these layers of RNA variation dramatically amplify functional output without increasing gene number, providing a coherent framework for linking static genomes to dynamic phenomes. By integrating conceptual models and biological examples, this review highlights RNA variation as a central organizing principle in genetics, with broad implications for evolution, development, and disease.
    Keywords:  RNA editing and modification; RNA variation; alternative processing; gene biotypes; genomic efficiency; transcript diversity
    DOI:  https://doi.org/10.7150/ijbs.135200
  78. Autophagy. 2026 Jun 24.
    Robust and sensitive ELISA detection of total and activated PRKN.
    Jens O Watzlawik, Bernardo A Bustillos, Claudia Rodriguez Martinez, Dennis W Dickson, Zbigniew K Wszolek, Owen A Ross, Wolfdieter Springer, Fabienne C Fiesel.
      Parkinson disease (PD) is closely linked to disruptions in mitochondrial quality control, a process regulated by the ubiquitin kinase PINK1 and the E3 ubiquitin ligase PRKN/parkin. Upon mitochondrial damage, PINK1 phosphorylates ubiquitin, which in turn recruits and activates PRKN. Full activation of PRKN is mediated by PINK1-dependent phosphorylation of PRKN at serine 65, which leads to widespread ubiquitination of mitochondrial substrates and amplifies the mitophagy response. Disruption of this pathway results in mitochondrial accumulation, oxidative stress, and neuronal death, all key mechanisms of PD pathogenesis. Genetic studies have shown biallelic loss-of-function mutations in PRKN are the most common cause of early-onset PD. Although the role of haploinsufficiency remains under investigation, PRKN protein becomes insoluble and inactive with aging or post-translational modifications, indicating that functional protein levels are a key determinant of disease risk. Reliable quantification of total and activated PRKN in samples has not been feasible, limiting research and clinical assessment. To address this, we developed and validated knockout (KO)-verified sandwich ELISA assays that quantify both total PRKN and PINK1-phosphorylated p-S65-PRKN. These assays provide absolute quantification of PRKN, improving functional diagnosis, and patient stratification in PD. Application of these methods established the concentration of PRKN in cells and in brain and revealed significant effects of a common genetic PRKN variant, further highlighting the importance of determining functional PRKN protein levels. The developed immunoassays complement previously established PINK1 and p-S65-Ub measurements, enhancing mechanistic insight into mitophagy and enabling effective monitoring of PD therapies and other neurodegenerative diseases.
    Keywords:  Autophagy; P-S65-PRKN; PARK2; PINK1; biomarker; mitochondria; mitophagy; parkin; parkinson disease; ubiquitin
    DOI:  https://doi.org/10.1080/15548627.2026.2694658
  79. J Zhejiang Univ Sci B. 2026 May 04. pii: 1673-1581(2026)06-0590-13. [Epub ahead of print]27(6): 590-602
    HENMT1: an RNA methyltransferase in biology and disease.
    Shanghong Jiang, Yongchao Zhao, Danrui Cui.
      HEN methyltransferase 1 (HENMT1) is an RNA methyltransferase that catalyzes 2'-O-methylation of P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) within the small RNA silencing pathway and methylates microRNAs (miRNAs). By stabilizing these RNA molecules, HENMT1 plays a pivotal role in regulating the biological processes that they target, thereby maintaining cellular homeostasis. Mutations in HENMT1 homologs across various species have been shown to alter biological traits and impair reproduction. HENMT1 mutations have been linked to infertility and tumor development in humans. This comprehensive review first introduces the structure and function of HENMT1 and its homologs, with a focus on elucidating the piRNA methylation process. Next, we examine the aberrant expression of HENMT1 in human cancers and its relationship with immune infiltration by analyzing the Cancer Genome Atlas (TCGA) database and tumor immune infiltration profiling, providing insights into the dysregulation of HENMT1 in diseases such as infertility and cancer. Finally, we discuss current knowledge and future perspectives on HENMT1's function in cancer progression.
    Keywords:  2'- O-Methylation; HEN methyltransferase 1 (HENMT1); Infertility; RNA methyltransferase; Tumor development
    DOI:  https://doi.org/10.1631/jzus.B2500059
  80. J Biochem Mol Toxicol. 2026 Jul;40(7): e70989
    Carboplatin Elicits ROS Responses and Potentially Regulates Translation Program in Cancer Systems.
    Qin Li, Si Qin, Liuxin Yang, Man Li, Xiang Li.
      Platinum-based chemotherapeutic agents display broad-spectrum and high anticancer activity, the primary target of which is nuclear DNA. During platinum chemotherapeutics, the steady-state levels of reactive oxygen species (ROS) are generally elevated. However, the pathways by which platinum drugs generate ROS and the biological responses still lack systematic studies. Taking carboplatin as an example, we found that both ROS and antioxidant enzyme expression were elevated, and multiple genes for mitochondrial translation and respiration were up-regulated to serve as contributors to ROS. Various genes for mitoribosome stress were also up-regulated, potentially controlling mitochondrial respiration and translation. The expression of single‑stranded DNA‑binding protein 1 (SSBP1), a mitochondrial translational regulator and a potential anti‑cancer target, was up‑regulated in carboplatin-treated cancer cells and in 22 tumor tissues, probably influencing the efficacy of chemotherapy. The potential crosstalk between mitochondrial translation and ROS response should be crucial for the clinical use of platinum drugs.
    Keywords:  anticancer; mitochondrial translation; platinum drugs reactive oxygen species; ribosome stress
    DOI:  https://doi.org/10.1002/jbt.70989
  81. Biogerontology. 2026 Jun 20. pii: 117. [Epub ahead of print]27(4):
    RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis.
    Qunhua Han, Shunmei Huang, Suisui Luo, Dianqiang Yang.
      Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and translation. Dysregulated RBP-RNA interactions have been closely associated with aging and age-related diseases. This review systematically summarizes the structural characteristics of RBPs and the evolution of methods used to study them. We focus on the molecular mechanisms of six key RBPs, namely HuR, AUF1, TTP, IGF2BP2, QKI, and LARP7, in the context of aging and age-related diseases. In addition, we discuss the regulatory functions of post-translational modifications of RBPs. Furthermore, we provide a multidimensional overview of RBP involvement in aging and age-related diseases through large language model (LLM)-based text-mining analysis. Our study provides a foundation for the comprehensive characterization of RBPs in aging and age-related diseases.
    Keywords:  Aging and age-related diseases; Large language model; Molecular mechanism; Post-translational modifications; RNA-binding proteins
    DOI:  https://doi.org/10.1007/s10522-026-10464-7
  82. Biology (Basel). 2026 Jun 08. pii: 897. [Epub ahead of print]15(12):
    Genome-Wide Characterization and Expression Profiling of Putative m6A Methylation Regulatory Proteins (Writers and Erasers) in Ginkgo biloba.
    Yuke Ma, Wenhui Guo, Han Wang, Jingjing Zhang, Meixiang Wei, Chaoyue Shi, Kongshu Ji, Qiong Yu.
      m6A is an important RNA modification involved in post-transcriptional regulation in plants. However, putative m6A writers and erasers in G. biloba remain poorly characterized. In this study, a total of 17 candidate m6A regulatory genes, including 8 writers and 9 erasers, were identified through genome-wide analysis. Phylogenetic and structural analyses indicated that these proteins are generally conserved, with some members showing potential functional divergence. Promoter analysis revealed abundant hormone- and stress-responsive cis-elements, and expression profiling showed tissue-specific patterns and dynamic responses to ABA, MeJA, and NaCl treatments, with erasers exhibiting greater transcriptional responsiveness than writers. In addition, protein interaction network and phase separation predictions suggested potential roles in RNA methylation-related processes. These results provide a foundation for further functional studies of m6A regulation in G. biloba.
    Keywords:  Demethylases; Ginkgo biloba; Methyltransferases; N6-methyladenosine; RNA epigenetics; abiotic stress
    DOI:  https://doi.org/10.3390/biology15120897
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