bims-spribo Biomed News
on Specialized ribosomes
Issue of 2026–10–11
fifteen papers selected by
Maxim Bouvet, Università di Torino
  1. Ribosome remodeling drives translation adaptation during viral infection and cellular stress.
  2. 40S ribosome remodeling triggers 18S rRNA U-tailing and DIS3L2-dependent decay.
  3. RSL24D1 links ribosome biogenesis to p53 activation in melanoma.
  4. Pyrrolysine supply and demand shapes the translational landscape in Methanosarcina acetivorans.
  5. Oligo(uridine) tailing and exonucleolytic decay drive 40S ribosome degradation in response to stress.
  6. Real-time single-molecule imaging in zebrafish embryos uncovers noncanonical translation.
  7. Temozolomide Induces Aberrant RNA Alkylation and Widespread Translational Repression.
  8. Rescue of ribosomal protein bL27 in Streptococcus pneumoniae TIGR4 by an alternate protease.
  9. Global and specific mechanisms stimulate mistranslation in cancer.
  10. You are what you eat and translate: Feeding the code to fight cancer and viruses.
  11. Bidirectional photoriboswitch for translational regulation in mammalian cells.
  12. ATP and α-ketoglutarate link nitrogen availability to TORC1-Npr1 signaling in yeast.
  13. Distinct protein synthesis requirements for coupled excitatory and inhibitory long-term co-plasticity in mouse hippocampus.
  14. Mesenchymal stem cells in ribosomal insufficiency lead to aberrant osteoblastic differentiation and altered hematopoiesis.
  15. tRF-3021a Promotes Apoptosis Resistance and Global Protein Synthesis in Cancer Cell Lines.
  1. Mol Cell. 2026 Oct 07. pii: S1097-2765(26)00629-5. [Epub ahead of print]
    Ribosome remodeling drives translation adaptation during viral infection and cellular stress.
    Hsin-Yu Tsai, Luochen Liu, Rebecca H Fleming, Julian Mintseris, Derrick Ekanayake, Jing A Guo, Xin Gu, Steven P Gygi, Amy S Y Lee.
      The ribosome is the highly conserved molecular machine that decodes mRNAs during protein synthesis. Here, we discover that, while traditionally thought to consist of a uniform set of proteins, ribosome composition is reprogrammed to adapt to intrinsic and external cellular perturbations. During infection of human cells by non-segmented negative-sense viruses, viral entry into cells recruits the large ribosomal subunit protein rpL40 to a non-canonical site on the small subunit of 80S ribosomes near the mRNA entry site. These specialized ribosomes preferentially bind viral mRNAs to drive enhanced viral protein synthesis that is critical for replication under host pressures. Unexpectedly, we find that viruses have co-opted this translation pathway from a previously unrecognized endogenous ribosome remodeling program in which metabolic stress alters ribosome structure to promote mRNA translation required for cell survival. Thus, ribosome remodeling is a conserved mechanism that enables dynamic protein synthesis across pathogen and cellular adaptation.
    Keywords:  cell stress; ribosome; ribosome heterogeneity; rpL40; translation regulation; virus
    DOI:  https://doi.org/10.1016/j.molcel.2026.09.008
  2. Mol Cell. 2026 Oct 09. pii: S1097-2765(26)00665-9. [Epub ahead of print]
    40S ribosome remodeling triggers 18S rRNA U-tailing and DIS3L2-dependent decay.
    Akruti Shah, Aaztli R Coria, Jennifer T Miller, Emilien Orgebin, Wilfried Guiblet, Acong Yang, Shuo Gu, Colin Chih-Chien Wu.
      Eliminating defective ribosomes through quality control is essential for accurate protein synthesis. However, the mechanisms that commit defective ribosomal subunits to decay remain poorly defined. Here, we identify a tandem mechanism in which ubiquitin-dependent ribosome remodeling and 18S rRNA uridylation lead to 40S ribosomal subunit decay. Specifically, we use an in vitro reconstitution system to show that the atypical kinase RIOK3 remodels 40S ribosomal subunits, thereby exposing the 3' end of 18S rRNA. Nanopore direct RNA sequencing reveals that this remodeling event promotes oligo-uridylation, generating uridylated 18S rRNA decay intermediates. Uridylated 18S rRNA is further degraded by the 3'-5' exoribonuclease DIS3L2. Moreover, DIS3L2-mediated exoribonucleolytic cleavage triggers endoribonucleolytic decay of the 18S rRNA, amplifying turnover. Together, our findings define a stepwise mechanism in which ribosome remodeling and RNA tailing commit defective 40S subunits to elimination, establishing a mechanistic framework for ribosome surveillance in mammalian cells.
    Keywords:  18S rRNA decay; DIS3L2; RIOK3; RNF10; TUT4/7; ribosome turnover; uridylation
    DOI:  https://doi.org/10.1016/j.molcel.2026.09.022
  3. Cancer Gene Ther. 2026 Oct 07.
    RSL24D1 links ribosome biogenesis to p53 activation in melanoma.
    Leonie Stahl, Sebastian Staebler, Anja K Bosserhoff.
      Melanoma cells exhibit elevated translation activity and rely on intact ribosomes to sustain their high protein synthesis demand. To support this process, efficient ribosome biogenesis is essential. RSL24D1 is a ribosome biogenesis factor required for late-stage maturation of the 60S ribosomal subunit. By ensuring correct ribosomal assembly, RSL24D1 supports global protein translation and maintains cellular homeostasis. Transcript and protein analyses revealed that RSL24D1 is upregulated in melanoma cells compared to normal human epidermal melanocytes. This overexpression correlates with reduced patient survival, suggesting an oncogenic role. Reduction of RSL24D1 expression impaired protein synthesis, decreased cell growth and resulted in the accumulation of unincorporated ribosomal proteins RPL5 and RPL11, which form the 5S RNP complex and inhibit the binding of MDM2 to p53. This inhibition stabilised p53 and activated downstream targets, including CDKN1A, resulting in G1 phase arrest and a senescence-like phenotype. These findings identify RSL24D1 as a critical component linking ribosome biogenesis to the p53 stress response. Targeting RSL24D1 creates a translational bottleneck, suppressing cell growth in p53 wild-type and p53-mutant cancer cells, highlighting it as a potential therapeutic target.
    DOI:  https://doi.org/10.1038/s41417-026-01089-6
  4. Proc Natl Acad Sci U S A. 2026 Oct 13. 123(41): e2614934123
    Pyrrolysine supply and demand shapes the translational landscape in Methanosarcina acetivorans.
    Grace D Britt, Daniel R Utter, Yeonsoo Park, Victoria J Orphan, Rodney Tollerson.
      The amber stop codon (UAG) can encode for pyrrolysine (Pyl) or be read as a stop codon by methylamine-metabolizing organisms including methanogenic archaea. The fate of UAG is decided during the decoding step of translation by competition between the pyrrolysine-aminoacylated transfer RNA (Pyl-tRNAPyl) and release factor. To further understand the consequences of pyrrolysine based genetic code expansion, we integrated RNA sequencing, tRNA charging analysis, and codon-resolved mono- and disome ribosome profiling in Methanosarcina acetivorans. During conditions of high pyrrolysine demand, we observed increased expression of the pyrrolysine biosynthetic operon with a concurrent increase in acylation of tRNAPyl and ribosome occupancy at UAG codons. During low pyrrolysine demand, the population of Pyl-tRNAPyl decreases and we observe a strong ribosome pausing signal during UAG decoding. We find that the dwell time on UAG codons is shorter during high demand, but ribosome collisions increase due to greater ribosome density on UAG-containing transcripts. Together, these results show how pyrrolysine demand modulates tRNA charging and controls elongation dynamics, clarifying the cellular consequences of decoding an ambiguous stop codon.
    Keywords:  Methanosarcina acetivorans; genetic code expansion; pyrrolysine; ribosome pausing; tRNA charging
    DOI:  https://doi.org/10.1073/pnas.2614934123
  5. Mol Cell. 2026 Oct 09. pii: S1097-2765(26)00664-7. [Epub ahead of print]
    Oligo(uridine) tailing and exonucleolytic decay drive 40S ribosome degradation in response to stress.
    Frances F Diehl, Allen R Buskirk, Rachel Green.
      Stresses like starvation trigger degradation of mature 40S ribosomes, requiring the coordinated breakdown of large, stable RNA-protein complexes. The atypical kinase RIOK3 orchestrates degradation by binding ubiquitylated 40S ribosomes and promoting rRNA decay. However, the mechanisms and factors that mediate rRNA decay remain unknown. Here we find that in response to starvation, RIOK3 recruits the terminal uridylyl-transferase TUT7 and the exonuclease DIS3L2 to 40S ribosomes. Sequencing analyses show that TUT7 adds oligo(uridine) tails to the 3' end of 18S rRNA in these ribosomes. DIS3L2 subsequently recognizes uridylated 18S rRNA and carries out 3'-5' decay. We identify major decay intermediates that undergo further uridylation in a process of iterative uridylation and decay. Loss of DIS3L2 impairs 18S rRNA decay during starvation and leads to accumulation of uridylated 18S rRNA. Together these findings define a mechanism for ribosome degradation in human cells in which oligo(uridine) tailing drives decay of rRNA from ribosomes.
    Keywords:  DIS3L2; RIOK3; RNA decay; Ribosome; TUT7; rRNA; starvation; stress response; uridylation
    DOI:  https://doi.org/10.1016/j.molcel.2026.09.021
  6. Sci Adv. 2026 Oct 09. 12(41): eaeb6883
    Real-time single-molecule imaging in zebrafish embryos uncovers noncanonical translation.
    Maëlle Bellec, Jie Liang, Kenny Mattonet, Tatsuya Morisaki, Margaux Lay, Hans-Martin Maischein, Damien Avinens, Vincent Martinet, Delphine Muriaux, Timothy J Stasevich, Jérémy Dufourt, Didier Y R Stainier.
      Precise spatiotemporal control of protein synthesis is essential during embryogenesis, yet directly measuring translation kinetics in vivo remains challenging in vertebrates. In particular, it remains unclear how translation efficiency is determined for key developmental regulators and which kinetic steps limit their production. Here, we used ALFA array-based nascent chain labeling combined with lattice light-sheet microscopy to visualize bmp2b translation in real time and at single-molecule resolution in early zebrafish embryos. When combined with MS2/MCP labeling to visualize all bmp2b messenger RNA (mRNAs), we found that only some of them are being actively translated, suggesting that limited mRNA translation competence contributes to overall translation efficiency. We found that bmp2b translation operates below a maximal initiation regime, as replacement of its untranslated regions (UTRs) with viral UTRs increases ribosome loading. Furthermore, the bmp2b, but not actb2, 5'UTR supports cap-independent translation with ribosome loading comparable to cap-dependent initiation. Together, this approach provides a quantitative in vivo framework to dissect translation kinetics during early vertebrate development.
    DOI:  https://doi.org/10.1126/sciadv.aeb6883
  7. bioRxiv. 2026 Sep 02. pii: 2026.09.01.748722. [Epub ahead of print]
    Temozolomide Induces Aberrant RNA Alkylation and Widespread Translational Repression.
    Jayden Rhodes, Abigail Grace Johnston, Katherine Marlow Brazell, Xisheng Liu, John L Hartman, Zhangli Su.
      Temozolomide (TMZ) is a frontline alkylating chemotherapy, yet its direct impact on RNA modification and global translation dynamics remains poorly understood. Here, we demonstrate that TMZ induces pervasive RNA alkylation causing severe translational impairment. TMZ directly deposits aberrant methyl groups onto single-stranded mRNA in vitro , creating physical lesions that lower translational efficiency. In glioblastoma cells, acute TMZ exposure triggers a rapid, widespread accumulation of m 7 G on cellular RNAs, leading to the significant attenuation of global protein synthesis. Nanopore direct RNA sequencing identified distinct guanine-specific error signatures and sequence context preferences associated with TMZ-induced damage. Using a quantitative yeast spike-in ribosome profiling strategy, we mapped this translational repression at transcript-level, revealing a global downregulation of translational efficiency. This widespread repression disproportionately targets highly interconnected networks essential for cellular proliferation, specifically chromosome organization. We show that the severity of this translational repression is driven by a transcript's coding guanine density, stability and translation initiation speed. Together, our findings suggest that TMZ-induced alkylation targets stable, highly translated, guanine-rich transcripts. This establishes aberrant RNA methylation and subsequent translational arrest as a potential mechanism of temozolomide cytotoxicity.
    DOI:  https://doi.org/10.64898/2026.09.01.748722
  8. bioRxiv. 2026 Aug 11. pii: 2026.08.10.744006. [Epub ahead of print]
    Rescue of ribosomal protein bL27 in Streptococcus pneumoniae TIGR4 by an alternate protease.
    Amarshi Mukherjee, Mohamed O Nasef, Patrick M Lindstrom, Nehaal Akavaram, Vipin Chembilikandy, Eriel Martinez, Carlos J Orihuela, Terje Dokland.
      Streptococcus pneumoniae is a major human respiratory pathogen. The bacterial 70S ribosome is a target of many clinically important antibiotics. The N-terminus of ribosomal protein bL27 extends into the peptidyl transferase center and contributes to the translation process. In Firmicutes, full length bL27 contains an 8-12 amino acid N-terminal extension that is absent from Gram-negative bacteria. This extension is cleaved by the protease Prp, which is absent from organisms lacking the extension. Prp-mediated cleavage of bL27 is essential in Staphylococcus aureus , and Prp has been proposed as a potential antibiotic target. Here, we show that in S. pneumoniae strain TIGR4, a Δ prp mutant remained viable, and produced ribosomes containing cleaved bL27, whereas deletion of prp was not tolerated in strain D39. These results suggested the presence of an alternate bL27-processing protease in TIGR4 that was absent from D39. Using a combination of genomics, proteomics and biochemical analyses, we identified this enzyme as the product of previously uncharacterized gene SP_1145 , encoding a protease that we named Ribosome rescue protease (Rrp). SP_1145 is carried on a mobile genetic element that is present in strain TIGR4, but absent from D39. Our findings shed light on an alternative mechanism for bL27 maturation, and indicate that some strains of S. pneumoniae harbor horizontally acquired redundant pathways for this essential ribosome processing step.
    DOI:  https://doi.org/10.64898/2026.08.10.744006
  9. Nat Cell Biol. 2026 Oct 05.
    Global and specific mechanisms stimulate mistranslation in cancer.
    Demi Wernaart, Amos Fumagalli, Mrittika Adhikary, Xiaodong Feng, Olaf Geintzer, Edwin S Kyei-Baffour, Onno B Bleijerveld, Liesbeth Hoekman, Ceri Zwart, Alexander Fish, Lisanne Giebel, Artur Burylo, Natalie Proost, Pierre-René Körner, Ferhat Alkan, Chao Yang, Janne Brouwer, Cecilia Anna Henriksen, Eric Westhof, Julien Champagne, Olaf van Tellingen, Marina Rodnina, Reuven Agami.
      Tryptophan codon-specific mistranslation, in the form of ribosomal frameshifting and tryptophan-to-phenylalanine (W > F) codon reassignments (substitutants), is induced in cancer cells by the limiting level of tryptophan imposed by anti-tumour immunity. While the oncogenic mitogen-activated protein kinase pathway drives frameshifting, whether substitutants are genetically regulated remains unknown. Here we screened for genes that control W > F substitutants following interferon-γ-mediated tryptophan shortage. This screen identified ADAR1, an enzyme that converts adenosine to inosine in double-stranded RNA molecules, and FTSJ1, an enzyme that 2'-O-methylates the anticodon region of several tRNAs. We demonstrate that ADAR1 sustains expression of key players in the ribosome quality control pathway, which in turn is essential for mistranslation events. FTSJ1, in contrast, specifically drives W > F mistranslation by methylation of tRNATrp to promote its binding to WARS1 loaded with phenylalanine instead of tryptophan. As ADAR1 and FTSJ1 levels are elevated in many cancer types, we propose that cancer cells deploy global and specific mechanisms to promote mistranslation in response to anti-tumour immunity.
    DOI:  https://doi.org/10.1038/s41556-026-02088-3
  10. Cell Metab. 2026 Oct 06. pii: S1550-4131(26)00381-5. [Epub ahead of print]38(10): 1949-1951
    You are what you eat and translate: Feeding the code to fight cancer and viruses.
    Adrianna Dabrowska, Davide Ruggero.
      How nutrients shape gene expression has remained a fundamental question. Wu et al.1 show that extracellular arginine directly remodels the tRNA-codon axis, controlling codon-dependent translation of major histocompatibility complex class I mRNA independently of canonical amino acid stress signaling. This nutrient-sensing mechanism regulates immunity in colorectal cancer and viral infection while revealing new opportunities for therapeutic intervention.
    DOI:  https://doi.org/10.1016/j.cmet.2026.09.006
  11. iScience. 2026 Oct 16. 29(10): 117671
    Bidirectional photoriboswitch for translational regulation in mammalian cells.
    Yaxin Hu, Cheuk Yin Li, Lala Fu, Yiang Sun, Mingji Zhang, Tak Marx Yau, Chuxiao Xiong, Peng Shi, Yi Kuang.
      Photoriboswitches are invaluable tools for synthetic biology because they provide direct, precise, and on-demand control of translation. While most existing photoriboswitches are predominantly one-directional, this study presents a bidirectional photoriboswitch platform capable of mimicking the orthogonal RNA-binding protein-mediated up-/downregulation of multiple mRNAs. Inspired by intein-based split protein reconstitution and light-induced protein dimerization, we first engineered a Light-OFF system that uses photodimerization to block intein reconstitution. We then validated that this Light-OFF system can function orthogonally with a Light-ON system that reconstitutes a different split intein pair under light. Together, a bidirectional photoriboswitch is generated, which senses light to orthogonally reconstitute RNA-binding proteins to tune the translation of their respective target mRNAs. We have demonstrated that the photoriboswitch produces bidirectional translation regulation. Importantly, the functional modules of the photoriboswitch can be easily altered to adapt for different purposes, allowing the bidirectional photoriboswitch to serve as a versatile tool for translation regulation.
    Keywords:  RNA-binding protein; bidirectional regulation; photodimerization; photoriboswitch
    DOI:  https://doi.org/10.1016/j.isci.2026.117671
  12. Mol Biol Cell. 2026 Oct 08. mbcE26050241
    ATP and α-ketoglutarate link nitrogen availability to TORC1-Npr1 signaling in yeast.
    Christopher Dereppe, Minoas Evangelinos, Elie Saliba, Viktória Ďurčová, Valentin Dubois, Ann Van Schepdael, Cédric Delporte, Bruno André.
      The TORC1 (Target of Rapamycin Complex 1) kinase complex coordinates eukaryotic cell growth and metabolism in response to nutrient availability. In yeast, one of the proteins under TORC1 control is the Npr1 kinase mediating nitrogen control of several plasma membrane transporters, yet the metabolic signals governing this pathway remain poorly understood. Here, we first investigated the previously described and unexpected activation of TORC1-Npr1 signaling upon acute glucose starvation. We show that this response occurs only under specific nitrogen conditions, notably in cells grown on proline or glutamine, and depends on increased ATP production driven by stimulated respiration. In proline-grown cells, this respiration is fueled by catabolism of α-ketoglutarate, while high α-ketoglutarate levels negatively affect TORC1-Npr1 activation. We next analyzed TORC1-Npr1 activation following NH4+ addition to proline-grown cells. Our results confirm that glutamine accumulation is not required for this activation and instead show that NH4+ assimilation is associated with a decrease in α-ketoglutarate levels and a sustained increase in ATP production, concomitant with TORC1-Npr1 activation. In cells lacking the NH4+-assimilating glutamate dehydrogenases, both increased ATP production and TORC1-Npr1 activation are impaired. Together, these findings identify ATP and α-ketoglutarate as important metabolic determinants of TORC1-Npr1 signaling in response to nitrogen availability.
    DOI:  https://doi.org/10.1091/mbc.E26-05-0241
  13. Neuropharmacology. 2026 Oct 05. pii: S0028-3908(26)00389-8. [Epub ahead of print] 111214
    Distinct protein synthesis requirements for coupled excitatory and inhibitory long-term co-plasticity in mouse hippocampus.
    Jadwiga Jabłońska, Dominika Orzoł, Dominika Ciurko, Grzegorz Wiera, Jerzy W Mozrzymas.
      The functioning of neuronal networks critically depends on the coordinated interaction between excitation and inhibition. The properties of glutamatergic and GABAergic synapses are finely tuned by network activity, and the heterosynaptic nature of inhibitory plasticity further emphasizes their functional coupling. Although the dependence of glutamatergic plasticity on protein synthesis is well established, the role of translation in inhibitory plasticity remains unclear. Herein, we investigated how protein synthesis supports the concurrent plasticity at inhibitory and excitatory inputs onto CA1 pyramidal neurons. To this end, we applied a high-frequency stimulation protocol of CA3-CA1 input combined with prolonged postsynaptic depolarization of principal cells. This induced both glutamatergic long-term potentiation (LTP) and inhibitory LTP (iLTP) at synapses formed by somatostatin-expressing interneurons onto pyramidal neurons. Although LTP was observed in slices from both juvenile (≤45 days) and adult (>45 days) mice, iLTP was only present in the adult group, revealing an unusual developmental profile. Moreover, in adult animals, excitatory LTP was required for the induction of iLTP but did not determine its magnitude. We found that bath application of translation inhibitor cycloheximide (CHX) strongly attenuated LTP and converted co-occurring iLTP into iLTD. However, when CHX was restricted to the recorded postsynaptic neuron, the initial phase of iLTP proceeded normally, but GABAergic currents gradually returned to baseline levels, indicating intact induction but impaired maintenance. In contrast, postsynaptic CHX left excitatory LTP unaffected. Together, these findings identify two distinct translational mechanisms: a postsynaptic one necessary for strengthening inhibition and a non-postsynaptic process required to potentiate excitation.
    Keywords:  GABA; cycloheximide; development; excitatory plasticity; inhibitory plasticity; pyramidal neuron; somatostatin interneuron; translation
    DOI:  https://doi.org/10.1016/j.neuropharm.2026.111214
  14. Haematologica. 2026 Oct 08.
    Mesenchymal stem cells in ribosomal insufficiency lead to aberrant osteoblastic differentiation and altered hematopoiesis.
    Hye Na Kim, Jacob Viduya, Aya Shibuya, Mark Wilkes, Kailen Mark, Y Lucy Liu, David C Shyr, Fabian Suchy, David Frankhouser, Laura Valine, Anju Goyal, Bertil E Glader, Kenneth Weinberg, Hiromitsu Nakauchi, Joy Y Wu, Kathleen M Sakamoto.
      Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome (IBMFS) characterized by macrocytic anemia. In addition to anemia, patients present with skeletal defects and an increased risk of osteosarcoma, suggesting dysregulated bone cell development. We found that ribosomal protein large subunit 11 (RPL11) haploinsufficiency affects bone marrow mesenchymal stem cells (MSCs), which are the precursors of osteoblasts that support lifelong hematopoiesis. Mouse and human DBA MSCs show decreased proliferation due to cytokinesis failure. Bulk RNA sequencing identified that DBA MSCs are enriched in gene sets associated with inflammation and bone remodeling that can affect surrounding hematopoietic cells. RNA sequencing further predicted aberrant bone maturation in DBA MSCs due to downregulation of the YAP pathway. In vitro differentiation assay confirmed that both mouse and human DBA MSCs fail to differentiate into osteoblasts compared with control MSCs. Activation of YAP signaling improved cell proliferation, morphology, and osteoblast differentiation potential in DBA MSCs. Lastly, we identified that DBA MSCs reduce the expansion of healthy hematopoietic stem and progenitor cells (HSPCs) through osteopontin. In contrast, DBA MSCs provide a favorable niche for DBA HSPCs and significantly increase the expansion of multipotent progenitors (MPPs). However, these MPPs have limited differentiation potential and do not mature into subsequent committed progenitors in the bone marrow. Taken together, this study provides an overview of the defective functions of DBA MSCs, informing follow-up studies to advance our understanding of niche-mediated pathogenic hematopoiesis of DBA.
    DOI:  https://doi.org/10.3324/haematol.2026.301254
  15. Mol Cancer Res. 2026 Oct 09.
    tRF-3021a Promotes Apoptosis Resistance and Global Protein Synthesis in Cancer Cell Lines.
    Fatemeh Esmaeili, Kumarjeet Banerjee, Ajay Chatrath, Divya Sahu, Yoshiyuki Shibata, Shekhar Saha, Pankaj Kumar, Zhangli Su, Anindya Dutta.
      tRNA-derived fragments (tRFs) are a relatively recently discovered class of small RNAs implicated in gene-regulation, particularly behaving as microRNA to degrade target mRNAs with seed-sequence matches, but there have been very few reports of a clear phenotypic role of these small RNAs in cancer cell growth and other properties. Here we report that in three different cancer cell lineages, tRF-3009a, tRF-3021a and tRF-3030a are required for cell invasion and migration. Of the three tRFs, tRF-3021a was uniquely required for cell proliferation and suppression of apoptosis. Interestingly, tRF-3021a knockdown decreases global protein synthesis prior to and independent of apoptosis in a number of cancer cell lines of different lineages. Mutation of tRF-3021a shows that the effect on protein synthesis is very dependent on specific sequences in the tRF. RNA-seq reveals that the results cannot be explained by tRF-3021a decreasing the levels of target mRNAs that carry seed sequence matches with the tRF. These data indicate that tRF-3021a supports cancer cell survival and particularly protein synthesis while promoting cellular invasion and migration. Implications: tRF-3021a promotes malignant cell phenotypes, sustains global protein synthesis and prevents spontaneous apoptosis.
    DOI:  https://doi.org/10.1158/1541-7786.MCR-26-0126
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