bims-spribo Biomed News
on Specialized ribosomes
Issue of 2026–09–20
seven papers selected by
Maxim Bouvet, Università di Torino
  1. Viral control of translation: rise of the ribosome.
  2. Ribosomal RNA transcription in normal and leukemic hematopoiesis.
  3. Transcript-wide m6A methylation defines the efficiency of cap-independent translation initiation.
  4. Eukaryotic AUG initiation contexts consist of a broad range of nucleotide patterns associated with distinct biological functions.
  5. Selective remodeling of snoRNA and sdRNA biology in glioblastoma.
  6. MiR-662 impairs C/D box snoRNA expression and rRNA 2'-O-ribose methylation marks.
  7. Programmed ribosomal frameshifting triggers translational stress to promote viral replication.
  1. J Virol. 2026 Sep 14. e0128226
    Viral control of translation: rise of the ribosome.
    Peter S Shen, Derek Walsh.
      Viruses have evolved a myriad of strategies to manipulate their host's protein synthesis machinery, studies of which uncovered many founding principles of translational control. Decades of research have established our now-extensive understanding of how these pathogens target the array of translation factors that recruit ribosomes and regulate scanning, start site selection, decoding, and termination. Meanwhile, the ribosome itself was largely regarded as a code-reading machine that lacks regulatory influence. Recent advances in cryo-electron microscopy and quantitative proteomics have upended this viewpoint by revealing the remarkable conformational and compositional plasticity that gives rise to functionally diverse and translationally selective ribosome populations in mammalian cells. Here, we discuss how viruses are once again at the forefront of this emerging field, often bypassing or rewiring host translation factors while directly controlling the ribosome's composition and intrinsic motions to selectively promote their non-canonical modes of translation. We offer cautionary perspectives on extra-ribosomal functions of ribosomal proteins, while highlighting the emergence of the 40S head domain as a dynamic platform targeted to control various translation processes, ranging from initiation to frameshifting, that expand viral coding capacity. Overall, we chart the rise of the ribosome from a passive player to an active regulatory hub at the center of viral translational control strategies.
    Keywords:  cryo-EM; ribosomal structure; ribosome; translational control; virus
    DOI:  https://doi.org/10.1128/jvi.01282-26
  2. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00081-5. [Epub ahead of print]170 1-48
    Ribosomal RNA transcription in normal and leukemic hematopoiesis.
    Jill A Henrich, Eleanor I Sams, Vikram R Paralkar.
      Hematopoiesis is governed by precisely coordinated transcriptional programs that balance hematopoietic stem cell (HSC) self-renewal with the ability to differentiate into multiple blood lineages. During normal hematopoiesis, cells maintain tight control over the level of ribosomal RNA (rRNA) transcription by RNA Polymerase I (Pol I) and over mature rRNA abundance (ribosomal subunits). Although the factors governing RNA Polymerase II (Pol II)-mediated gene expression and their roles in cell fate determination are well characterized, far less is known about the regulation of rRNA transcription and ribosome abundance. Little is known also about how ribosome numbers contribute to hematopoietic cell fate. This review summarizes current literature on the mechanisms by which hematopoietic cell types fine-tune rRNA transcription and ribosomal subunit abundance throughout cell fate trajectories, and how dysregulation of these processes contributes to acute myeloid leukemia (AML).
    Keywords:  Hematopoiesis; Leukemia; Nucleolus; RNA polymerase I (Pol I); Ribosomal DNA (rDNA); Ribosomal RNA (rRNA); Ribosome biogenesis; Ribosomes; rRNA transcription
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.06.008
  3. RNA. 2026 Sep 17. pii: rna.081017.126. [Epub ahead of print]
    Transcript-wide m6A methylation defines the efficiency of cap-independent translation initiation.
    Egor A Smolin, Andrey I Buyan, Dmitry N Lyabin, Anton A Buzdin, Ivan V Kulakovskiy, Irina A Eliseeva.
      N⁶-methyladenosine (m⁶A) plays an important role in translation control and, particularly, in cap-independent initiation. The impact of m⁶A is usually studied in the context of its location in the transcripts, but the global impact of m⁶A along mRNAs remains unclear. Here, we combined ribosome profiling under conditions of mTOR inhibition and m⁶A mapping to identify distinct subsets of mRNAs that differ in their sensitivity to the suppression of cap-dependent initiation. We found that the sensitivity strongly correlated with the total m⁶A methylation of the transcripts. Further, upon decreased mTOR activity, m⁶A methylation facilitated the enhanced association of mRNAs with components of the eIF4F complex. Thus, the efficiency of cap-independent translation initiation is primarily defined not by precise localization but by the total level of m⁶A methylation, and m⁶A has a compensatory role in maintaining translation when the canonical cap-dependent pathway is impaired. Our findings underscore the significance of contemplating global m⁶A methylation status as a pivotal element in translational control, particularly under stress or signaling perturbations.
    Keywords:  Ribo-Seq; cap-dependent initiation; m6A; mTOR inhibition
    DOI:  https://doi.org/10.1261/rna.081017.126
  4. Cell Rep. 2026 Sep 11. pii: S2211-1247(26)01064-8. [Epub ahead of print]45(9): 117986
    Eukaryotic AUG initiation contexts consist of a broad range of nucleotide patterns associated with distinct biological functions.
    Antonin Tidu, Paulo J da Costa, Laurence Despons, Eric Westhof, Gilbert Eriani, Franck Martin.
      In eukaryotes, translation initiation is extensively modulated by cis-regulatory sequences located on the mRNA along with trans-acting factors which influence the lifetime of the codon-anticodon interaction in the P site of the scanning 43S complex and eventually control ribosome assembly. Here, we analyzed sequences around AUG start codons to account for mutually dependent or mutually exclusive nucleotide combinations that influence start codon recognition. By comparing the initiation contexts of annotated coding sequences in six model eukaryotes, we show that their nucleotide features are highly species-specific. Searching for accurate consensus nucleotide patterns around AUG start codons identifies multiple nucleotide patterns rather than a single consensus sequence in each eukaryote. Importantly, these patterns highlight distinct nucleotide features around the conserved purine at position -3 across eukaryotes, known to strongly influence initiation efficiency. Finally, computing a species-specific score for any AUG context shows that these diverse nucleotide features associate with specific biological functions.
    Keywords:  5′UTR; AUG nucleotide context; CP: molecular biology; Kozak consensus; ribosome; start codon selection; translation initiation
    DOI:  https://doi.org/10.1016/j.celrep.2026.117986
  5. Front Cell Dev Biol. 2026 ;14 1925311
    Selective remodeling of snoRNA and sdRNA biology in glioblastoma.
    Hongtao Yin, Meiying Mu, Zhuoqun Wang.
      Small nucleolar RNAs (snoRNAs) are best known as guide RNAs for ribosomal RNA modification, but accumulating evidence indicates that their biology extends beyond canonical ribosome maturation. Across GBM-specific and broader glioma studies, snoRNAs, snoRNA-derived RNAs (sdRNAs), and associated small nucleolar ribonucleoprotein components are emerging as regulators of malignant cell states. This review frames GBM-associated snoRNA and sdRNA alterations as a cell-biological remodeling process that links ribosome biogenesis, metabolic adaptation, treatment response, and extracellular-vesicle output. Across currently available GBM and broader glioma studies, tumor-restraining C/D-box snoRNAs, including SNORD76, SNORD47, SNORD44, and SNORD113-3, tend to be reduced, and restoration of several of these molecules suppresses malignant phenotypes in their respective experimental systems. Conversely, tumor-supporting snoRNA-associated activities, including the U3-PHAX-DNA-PKcs-TRIM24 complex, a U3-derived small RNA acting through ZBTB7A, and preprint-based H/ACA snoRNA/snoRNP activity involving dyskerin, are maintained, increased, or functionally co-opted in specific GBM-related contexts. These alterations converge on three recurrent cellular contexts: translational capacity, glucose and glycolipid metabolism, and survival under radiotherapy or temozolomide. Treatment-associated senescence may also reshape extracellular-vesicle snoRNA cargo, with SNORA49 detected in a small longitudinal plasma series, although this remains exploratory rather than a validated liquid-biopsy marker. We also emphasize the need to distinguish snoRNAs and sdRNAs from their SNHG host transcripts, because these molecular entities have distinct biogenesis and mechanisms. Together, these studies suggest a context-dependent pattern of snoRNA and sdRNA dysregulation across GBM and related glioma models, with the strength of evidence varying among individual molecular axes. SnoRNAs and sdRNAs should be viewed as an emerging regulatory layer in GBM rather than as established therapeutic targets. Future work should validate molecule-specific snoRNA and sdRNA axes in disease-relevant models and determine whether extracellular-vesicle snoRNAs provide reproducible readouts of treatment-associated cell states.
    Keywords:  extracellular vesicles; glioblastoma; liquid biopsy; ribosome biogenesis; small nucleolar RNA (snoRNA); snoRNA-derived RNA (sdRNA); therapy resistance; tumor metabolism
    DOI:  https://doi.org/10.3389/fcell.2026.1925311
  6. BJC Rep. 2026 Sep 17. pii: 47. [Epub ahead of print]4(1):
    MiR-662 impairs C/D box snoRNA expression and rRNA 2'-O-ribose methylation marks.
    Charlotte Filossi, Caroline Isaac, Mariam Jaafar, Philippe Clézardin, Caroline Moyret-Lalle, Virginie Marcel, Margherita Puppo.
       BACKGROUND: MiR-662 overexpression has been reported to promote breast cancer metastatic progression and to impair the expression of genes encoding for proteins involved in translation, ribosome biogenesis and ribosome processing (Puppo et al., 2023); however, the relationship between miR-662 and the translational machinery was not further investigated at the time.
    METHODS: MiR-662 was overexpressed in MDA-MB-231-luc2 (NW1) human breast cancer cells. Global protein synthesis was analyzed using polysome profiles. Potential defects in rRNA 47S precursor biogenesis were evaluated by Northern blot. C/D box snoRNA (SNORD) expression was quantified by a medium-throughput RT-qPCR microfluidic dynamic array. rRNA 2'O-ribose methylation (2'Ome) was profiled using RiboMethSeq.
    RESULTS: No changes in rRNA synthesis, processing, or maturation were observed upon miR-662 overexpression. In contrast, a marked reduction in the ratio of polysomal to free ribosomal fractions was observed, indicating an impaired mRNA engagement into translation. Interestingly, a drastic decrease in SNORD levels (but not of their host genes) and a global decrease in rRNA 2'Ome was observed upon miR-662 overexpression.
    CONCLUSIONS: The involvement of miRNAs in snoRNA-induced modulation in rRNA epitranscriptomic marks might be a novel mechanism of fine regulation of the ribosome composition with possible repercussions on breast cancer metastatic progression.
    DOI:  https://doi.org/10.1038/s44276-026-00247-5
  7. Cell. 2026 Sep 14. pii: S0092-8674(26)01004-4. [Epub ahead of print]
    Programmed ribosomal frameshifting triggers translational stress to promote viral replication.
    Audrey Xavier, Melinda Kolling, Ashley M Bourke, Thorsten Mosler, Cristian Prieto-Garcia, Emil Karaulanov, Michaela Reissland, Michel Tassetto, Damian Kim, Katleen Klaassen, Katharina Grikscheit, Emma Torbica, Verena Dederer, Jonas Busam, Rubina Kazi, Ruth Olmer, Srinivas Reddy Pallerla, Sebastian Mathea, Markus E Diefenbacher, Kathi Zarnack, Denisa Bojkova, Marek Widera, Ranen Aviner, Raul Andino, Sandra Ciesek, Ivan Dikic.
      Programmed ribosomal frameshifting (PRF) is a conserved viral strategy for expressing polyproteins from compact genomes. Although PRF is traditionally viewed as a structural mechanism, here we show that it functions as a regulatory signal that rewires host translation in favor of viral replication. A minimal SARS-CoV-2 PRF element is sufficient to activate the GCN2 arm of the integrated stress response (ISR) independently of the canonical ISR sensor ZAKα. This activation serves as a temporal switch during early infection to shut off host translation and is required for viral propagation in cells and human airway organoids. Proteomic and genetic screens identify DRG1 and IGF2BP3 as key mediators of PRF-induced GCN2 activation. We further show that this PRF-GCN2 axis is conserved in human immunodeficiency virus (HIV)-1 and West Nile virus, highlighting its broad relevance across RNA viruses. These findings reveal a sophisticated mechanism of viral translational control, highlighting PRF as a stress-inducing module that enhances viral replication.
    Keywords:  RNA virus; cellular stress; host-pathogen interactions; integrated stress response; programmed ribosomal frameshifting; ribosome collision; translation; virology
    DOI:  https://doi.org/10.1016/j.cell.2026.08.031
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