bims-mirnam Biomed News
on Mitochondrial RNA metabolism
Issue of 2026–09–20
six papers selected by
Hana Antonicka, McGill University
  1. L-Cysteine and N-Acetylcysteine Supplementation Improves Clinical Outcome in a Patient With COXPD10.
  2. LACTB2 Promotes the Growth and Migration of Non-Small Cell Lung Cancer By Regulating Mitochondrial Function.
  3. Experimental and Computational Approaches to Identify RNA-Protein Interactions.
  4. R-Loop Modification and Quantification by Dot Blot.
  5. The RNA structural code: orchestrating gene expression and enabling precision therapies.
  6. Cyclosporin A triggers a RIG-I-mediated interferon response through multiple cellular processes.
  1. Am J Med Genet A. 2026 Sep 17.
    L-Cysteine and N-Acetylcysteine Supplementation Improves Clinical Outcome in a Patient With COXPD10.
    Nishitha R Pillai, Sara A Elsbecker, Grace Bronken McCarthy, Kaitlin Weisshappel, Peter Karachunski, Fernando Scaglia.
      MTO1 is a nuclear gene that encodes a mitochondrial protein essential for modifying mitochondrial transfer RNAs (tRNAs) and stabilizing codon-anticodon interactions to ensure accurate and efficient mitochondrial protein synthesis and oxidative phosphorylation. Mitochondrial tRNA translation optimization 1 (MTO1) plays an important role in the mitochondrial tRNA taurinomethylation modification by using the amino acid taurine, obtained from cysteine metabolism, at the wobble position U34 of the anticodon loop. Biallelic pathogenic variants in MTO1 cause combined oxidative phosphorylation deficiency 10 (COXPD10) (OMIM#614702). In the severe end of the spectrum, COXPD10 is characterized by infantile-onset hypertrophic cardiomyopathy and lactic acidosis with perinatal mortality when associated with nonsense and frameshift variants. The extra cardiac phenotypes include muscle hypotonia, feeding difficulties, psychomotor delay, optic atrophy, encephalopathy, and seizures. Currently, there is no targeted treatment for this condition aside from supportive care. Herein, we report a 22-month-old child, diagnosed early with a genotype predictive of severe COXPD10, who was initiated on treatment with L-cysteine and N-acetylcysteine (NAC) early in life and did not develop cardiac manifestations. This outcome suggests a potential benefit and improved clinical outcome with early disease-specific treatment initiation.
    Keywords:   MTO1 ; COXPD10; L‐cysteine; NAC; N‐acetylcysteine; cardiomyopathy; combined oxidative phosphorylation deficiency 10; cysteine
    DOI:  https://doi.org/10.1002/ajmg.a.70299
  2. Mol Carcinog. 2026 Sep 15.
    LACTB2 Promotes the Growth and Migration of Non-Small Cell Lung Cancer By Regulating Mitochondrial Function.
    Jie Zhang, Qian Chen, Yuanyuan Wu, Yajing Han, Yong Li.
      Lung cancer remains one of the most commonly diagnosed cancers and the leading cause of cancer-related mortality worldwide. As a mitochondrial matrix protein, the role of β-lactamase-like protein 2 (LACTB2) is unclear in non-small cell lung cancer (NSCLC). In this study, we show that LACTB2 expression enhances the cell viability, anchorage-independent growth, migration and epithelial-mesenchymal transition(EMT) of NSCLC cells. Mechanistically, LACTB2 binds to mitochondrial DNA (mtDNA) and activates mitochondrial RNA (mtRNA) expression. Silencing LACTB2 induces mitochondrial dysfunction, which correlates with impaired proliferation, migration, and EMT in NSCLC cells. Furthermore, depletion of LACTB2 results in an increased expression of p53 and cleaved-PARP, indicating that LACTB2-mediated mitochondrial dysfunction activates the mitochondrial retrograde signaling-p53 pathway to regulate apoptosis in A549 cells. Additionally, we found that high LACTB2 expression is statistically correlated with poor overall survival in NSCLC patients, and silencing LACTB2 inhibits tumor growth in xenograft mouse models. In summary, our findings reveal that LACTB2 plays a critical role in NSCLC progression by modulating mtRNA expression and mitochondrial function. Therefore, the LACTB2-mtDNA-mitochondrial dysfunction axis may serve as a novel target for diagnosis and treatment of NSCLC.
    Keywords:  LACTB2; NSCLC; growth; migration; mitochondrial dysfunction
    DOI:  https://doi.org/10.1002/mc.70180
  3. Cells. 2026 Aug 27. pii: 1546. [Epub ahead of print]15(17):
    Experimental and Computational Approaches to Identify RNA-Protein Interactions.
    Brigette Romero, Jadira Aurora Fuentes Bautista, Victoria Beringer, Maryia Hrynashka, Vijay Parashar, Mona Batish.
      RNA-binding proteins (RBPs) are essential regulators of RNA metabolism and gene expression, influencing processes such as splicing, stability, localization, and translation. Despite their critical roles in health and disease, including cancer, identifying RNA-protein interactions remains challenging due to technical limitations and biases of existing methods. Here we review and compare experimental techniques-including in vitro affinity purification, in vivo crosslinking, and proximity labeling-and computational prediction tools for RBP identification. We assess their strengths, limitations, and applicability across biological contexts, emphasizing the benefits of integrating experimental and computational strategies. Our analysis provides practical guidelines for selecting appropriate methodologies tailored to different cell types and research goals. These insights aim to facilitate more accurate mapping of RNA-protein interactomes, thereby advancing understanding of RBP functions and supporting the development of novel therapeutic interventions targeting RNA-protein complexes.
    Keywords:  RBP identification; RNA-binding proteins; RNA-centric and protein-centric approaches; RNA–protein interactions; computational prediction methods; crosslinking; experimental identification methods; proximity labeling
    DOI:  https://doi.org/10.3390/cells15171546
  4. Bio Protoc. 2026 Sep 05. 16(17): e5806
    R-Loop Modification and Quantification by Dot Blot.
    Taehwan Yang, Yi-Ru Li, Blerta Xhemalçe.
      RNA modifications and their "writer," "eraser," and "reader" proteins are emerging as key regulators of gene expression and DNA repair through dynamically regulating RNA:DNA hybrids, or R-loops, during transcription. Therefore, it is paramount to develop rigorous techniques for accurate analysis of R-loop modifications. A convenient method for analyzing RNA modifications within total RNA is by dot blot with specific RNA modification antibodies; however, analysis of the modification of the RNA moiety within R-loops presents specific challenges. Here, we provide a detailed protocol for the production or purification of DNA containing R-loops in vitro and from cells, and the analysis of the RNA moiety modifications by dot blot. The DNA containing R-loops is treated with either mock or RNase H, which specifically degrades the RNA within RNA:DNA hybrids, to control for the specificity of the signal as originating from R-loops. Known quantities of the mock or RNase H-treated DNA are then spotted on three membranes, each blotted with antibodies that recognize double-stranded DNA, RNA:DNA hybrids, or the specific RNA modification antibodies of interest, such as m6A or ac4C. Thus, this protocol is useful to both biochemists and cell biologists with scientific interests at the intersection of R-loops and epitranscriptomics. Key features • R-loops produced via in vitro transcription of R-loop-forming DNA sequences can serve as substrates for biochemical assays, quantification standards, or antibody specificity controls. • R-loop-containing DNA can be purified from cells after gene editing or various treatments to analyze how global R-loop levels and modifications are regulated. • This protocol was initially applied to the study of the role of NAT10 and ac4C modification of the RNA moiety within R-loops in human cells. • Requires 4-7 days to complete, depending on the origin of R-loops (in vitro transcription vs. from cells).
    Keywords:  Dot blot; Epitranscriptomics; NAT10; R-loop; ac4C
    DOI:  https://doi.org/10.21769/BioProtoc.5806
  5. Acta Pharmacol Sin. 2026 Sep 14.
    The RNA structural code: orchestrating gene expression and enabling precision therapies.
    Nan-Nan Fang, Qu-Bo Zhu.
      Following transcription, RNA undergoes hierarchical folding mediated by base pairing and long-range interactions, forming diverse dynamic structures such as local helices, loops, bulges, pseudoknots, G-quadruplexes, riboswitches, and higher-order conformations. These structures function as molecular switches that are recognized by RNA-binding proteins and regulatory factors, thereby precisely controlling the spatiotemporal dynamics of posttranscriptional gene expression. Emerging evidence indicates that aberrant RNA structural dynamics are closely associated with diverse human diseases. RNA-targeted therapeutic strategies, characterized by high specificity, programmability, and broad potential, have emerged as a promising next-generation therapeutic modality beyond conventional small-molecule and antibody-based therapies. Although current RNA-targeted approaches have focused primarily on gene silencing, strategies for enhancing endogenous gene expression are increasingly demonstrating substantial translational potential. In this review, we systematically summarize posttranscriptional gene regulation mechanisms mediated by RNA structural diversity, with a particular emphasis on the roles of RNA structures in alternative splicing, RNA localization and transport, translation, and RNA degradation. We further discuss recent advances, current challenges, and emerging clinical prospects of RNA-targeted therapeutic strategies in human diseases. Overall, this review provides a comprehensive overview of RNA structure‒function relationships and highlights their implications for precision medicine and the development of next-generation RNA-based therapeutics.
    Keywords:  RNA structure; RNA-targeted therapy; gene expression regulation; non-coding RNA; post-transcriptional control; precision medicine
    DOI:  https://doi.org/10.1038/s41401-026-01925-3
  6. Sci Rep. 2026 09 16. pii: 28863. [Epub ahead of print]16(1):
    Cyclosporin A triggers a RIG-I-mediated interferon response through multiple cellular processes.
    Lars Meier, Martin Schauflinger, Pauline Neubecker, Dennis Freisem, Lena Gimpl, Michelle Gellhorn Serra, Helene Hoenigsperger, Benjamin Rupf, Susanne Herold, Stefan Bauer, Konstantin M J Sparrer, Stephan Becker, Lucie Sauerhering.
      The development of broad-spectrum antiviral agents is essential for preparedness against emerging viruses with pandemic potential. Cyclosporin A (CsA), a clinically approved immunosuppressant, has been shown to exert antiviral activity against a wide range of viruses. Recent evidence suggests that this effect is partially mediated through the induction of interferon lambda (IFN-λ), which in turn stimulates a set of interferon-stimulated genes (ISGs) that establish an antiviral cellular state. However, the molecular mechanisms underlying IFN-λ induction by CsA have remained poorly understood. Here, we demonstrate that CsA triggers a retinoic acid-inducible gene I (RIG-I)-dependent activation of the IFN-λ/ISG signaling axis. This is accompanied by the upregulation of mitochondrial double-stranded RNA (dsRNA). Importantly, we show that CsA causes pronounced alterations in the mitochondrial cristae network. CsA also impairs autophagy, as evidenced by reduced autophagosomal membrane formation and increased levels of the autophagy marker p62. Supporting a functional link, treatment with the autophagy inducer Torin-1 reverses CsA-induced dsRNA accumulation, IFN-λ expression and ISG transcription. Together, our data indicate that the antiviral activity of CsA is partially driven by converging cellular processes involving mitochondrial remodeling, dsRNA accumulation, and impaired autophagy, which collectively activate the RIG-I/IFN-λ/ISG axis, offering mechanistic insights with therapeutic implications.
    Keywords:  Cyclosporin A (CsA); Drug repurposing; Mitochondria; Type III interferon
    DOI:  https://doi.org/10.1038/s41598-026-68563-x
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