bims-spribo Biomed News
on Specialized ribosomes
Issue of 2026–09–06
eleven papers selected by
Maxim Bouvet, Università di Torino
  1. Rewiring the ribosome to translate proteins encoded in its own RNA.
  2. Translational control by RPL22L1-specific ribosomes enhances DNA repair and chemoresistance.
  3. Ribosomal RNA methylation by GidB modulates discrimination of mischarged tRNA.
  4. Ribosomal architecture and rRNA modification landscape in the tick-borne parasite Babesia divergens.
  5. Isolation and Analysis of Bacterial Ribosomes Through Sucrose Gradient Ultracentrifugation.
  6. Ribo-ITP enables identification of translons from limited input samples.
  7. Fluorescence-Based mRNA Translation Reporter.
  8. Unbiased screen of human transcriptome reveals an unexpected role of 3'UTRs in translation initiation.
  9. Genetic dissection of human ABCE1 in yeast reveals separable requirements for ribosome recycling and suppression of aberrant reinitiation.
  10. An Epstein-Barr virus-encoded snoRNA directs 2'-O-methylation of human rRNAs to control translation and the viral lytic switch.
  11. RNA Labeling of Nucleolar Transcripts by 5-Ethynyl Uridine Click Chemistry.
  1. Nature. 2026 Sep 02.
    Rewiring the ribosome to translate proteins encoded in its own RNA.
    Kasra Alizadeh, Dorota Klepacki, Nora Vázquez-Laslop, Alexander S Mankin.
      Cellular protein synthesis relies on random encounters between ribosomes and mRNAs, limiting optimization of the translation machinery for production of a single protein-a key need in biotechnology. One potential solution is integrating the protein-coding sequence into the ribosome itself, thereby committing the ribosome to synthesis of a single polypeptide. The feasibility of such integration could also address a long-standing challenge in RNA world models: explaining how early protein synthesis could function reliably despite the scarcity and poor organization of its components1. Whether a ribosome can translate its own ribosomal RNA (rRNA) has remained unclear. Here we show that bacterial ribosomes can synthesize proteins encoded within their own RNA. We engineered a chimeric messenger-ribosomal RNA (mrRNA) by appending a protein-coding sequence to 16S rRNA. The hybrid mrRNA assembles into a small ribosomal subunit that binds to the large subunit to form Ribo-M, a ribosome capable of translating mrRNA-encoded proteins. Translation is abolished by mutations or antibiotics that impair the function of the small subunit, demonstrating that mrRNA translation is carried out in cis by ribosomes assembled on the chimeric mrRNA. Incorporating mrRNA into a ribosome with tethered subunits yielded Ribo-TM, in which encoding, decoding and peptide synthesis are united within a single RNA scaffold. These findings establish the mechanistic feasibility of a ribosome translating its own rRNA in vivo and in vitro, offering a versatile platform for orthogonal protein production and insights into the origin of translation.
    DOI:  https://doi.org/10.1038/s41586-026-10962-1
  2. Nat Commun. 2026 08 04. pii: 9367. [Epub ahead of print]17(1):
    Translational control by RPL22L1-specific ribosomes enhances DNA repair and chemoresistance.
    Saisai Wei, Wentao Yu, Yilin Shen, Yu Qian, Ye Wang, Tiezheng Li, Jiaqi Cao, Xiangwei Gao, Xiujun Cai.
      Ribosome heterogeneity has emerged as a regulatory layer in gene expression, yet its biological roles in cancers remain poorly characterized. Here, we identify RPL22L1, a paralog of the ribosomal protein RPL22, as a key modulator of DNA damage response (DDR) in colorectal cancer cells. DNA damage induces RPL22L1 upregulation and ribosomal incorporation, forming RPL22L1-specific ribosomes. Ribosome profiling reveals that RPL22L1-containing ribosomes preferentially translate mRNAs with highly structured 5' untranslated region (5'UTR). In particular, RPL22L1 enhances the translation of ATRX through a cap-independent mechanism. ATRX subsequently recruits DNA-PKcs to DNA damage sites, thereby enhancing the DNA repair capacity. RPL22L1 loss creates exploitable DDR vulnerabilities, sensitizing cancer cells to cisplatin and PARP inhibitors in vitro and in vivo. Collectively, these findings uncover a specialized ribosome-mediated translational program in DDR and highlight RPL22L1 as a potential therapeutic target in DDR-based cancer therapy.
    DOI:  https://doi.org/10.1038/s41467-026-76283-z
  3. Elife. 2026 Sep 04. pii: RP102752. [Epub ahead of print]13
    Ribosomal RNA methylation by GidB modulates discrimination of mischarged tRNA.
    Zhuo Bi, Yu-Xiang Chen, Iris D Young, Mohamad T Dandan, Hemant Joshi, Hong-Wei Su, Yuemeng Chen, Jiayao Hong, James S Fraser, Babak Javid.
      Despite redundant cellular pathways to minimize translational errors, errors in protein synthesis are common. Pathways and mechanisms to minimize errors are classified as pre-ribosomal or ribosomal. Pre-ribosomal pathways are primarily concerned with the appropriate charging of tRNAs with their cognate amino acids. By contrast, the ribosomal decoding center is considered 'blind' to mischarged tRNAs since these have cognate codon•anti-codon pairing. Here, we identified that in mycobacteria, deletion of the 16S ribosomal RNA methyltransferase gidB led to increased ribosomal discrimination of mischarged tRNAs. Discrimination only occurred in mycobacteria enriched from environments or genetic backgrounds with high rates of mistranslation. GidB deletion was necessary, but not sufficient for reducing mistranslation due to misacylation. Analysis of new cryo-EM structures of the M. smegmatis ribosomes derived from wild-type and gidB-deleted strains point to the interaction between the base methylated by GidB on the 16S RNA and an asparagine on the ribosomal S12 protein that, when mistranslated to aspartate, may be involved in altering translational fidelity. Our data suggest a mechanism by which mycobacterial ribosomes can discriminate mischarged tRNAs and that 16S rRNA differential methylation by GidB may act to prevent catastrophic translational error.
    Keywords:  GidB; Mycobacterium; antibiotic tolerance; chromosomes; gene expression; infectious disease; microbiology; mistranslation; ribosome
    DOI:  https://doi.org/10.7554/eLife.102752
  4. Nat Commun. 2026 Aug 06. pii: 9475. [Epub ahead of print]17(1):
    Ribosomal architecture and rRNA modification landscape in the tick-borne parasite Babesia divergens.
    Cristina Gutierrez-Vargas, Lee S Izhaki-Tavor, Diana G Calvopina-Chavez, Caroline D Keroack, Pablo Copello, Manoj T Duraisingh, Mélissa Léger-Abraham.
      Babesia are tick-borne intracellular apicomplexan parasites that infect a wide range of wild and domestic animals (e.g., cattle), resulting in significant economic losses to the livestock industry. Humans are considered accidental hosts for a few Babesia species. Babesia microti and B. divergens are the most prevalent causes of human babesiosis that are showing a broadening geographic distribution. Due to the complex life cycle of Babesia species, their survival depends on the precise control of gene expression, which is primarily regulated by epigenetic, transcriptional, and post-transcriptional mechanisms. High-resolution structural information on key components of the translation machinery, such as ribosomes, could aid in the development of antiparasitic drugs. Here, we report cryogenic electron microscopy ribosome structures from B. divergens, showing associated tRNAs, an mRNA fragment, and RACK1, a signaling scaffold crucial to translation regulation. Density map analysis displays ribosome regions at high resolution, which, when combined with nanopore sequencing, enabled the comprehensive identification of rRNA modifications. The rRNA modifications localize not only to the reduced B. divergens rRNA expansion segments but also to functionally essential ribosomal sites.
    DOI:  https://doi.org/10.1038/s41467-026-75282-4
  5. Methods Mol Biol. 2026 ;3051 301-313
    Isolation and Analysis of Bacterial Ribosomes Through Sucrose Gradient Ultracentrifugation.
    Ricardo F Dos Santos, Cátia Bárria, Alda F Q Silva, João P Sousa, Cecília M Arraiano, José M Andrade.
      Ribosomes are large macromolecular complexes responsible for the translation process. During the course of ribosome biogenesis and protein synthesis, extra-ribosomal factors interact with the ribosome or its subunits to assist in these vital processes. Here we describe a method to isolate and analyze not only bacterial ribosomes but also their associated factors, providing insights into translation regulation. This detailed protocol allows the separation and monitoring of the ribosomal species and their interacting partners along a sucrose density gradient. Simultaneously, fractionation of the gradient allows for the recovery of 70S ribosomes and its subunits enabling a wide range of downstream applications. This protocol can be easily adapted to ribosome-related studies in other species or for separating other macromolecular complexes.
    Keywords:  Ribosome isolation; Ribosome profiles; Ribosomes; Sucrose gradient; UV analysis; Ultracentrifugation
    DOI:  https://doi.org/10.1007/978-1-0716-5372-2_18
  6. Nat Commun. 2026 07 31. pii: 9264. [Epub ahead of print]17(1):
    Ribo-ITP enables identification of translons from limited input samples.
    Vighnesh Ghatpande, Uma Paul, Logan Persyn, Yifan Tian, MacKenzie A Howard, Can Cenik.
      In the last decade, an unexpectedly large number of translated regions (translons) have been discovered using ribosome profiling and proteomics. Translons can act as regulatory elements or encode functional micropeptides. However, identification of translons has been limited to cell lines or large organs due to high input requirements for conventional ribosome profiling and mass spectrometry. Here, we address this input limitation using Ribo-ITP on difficult-to-collect samples such as microdissected hippocampal tissues and single preimplantation embryos to identify thousands of translons. To test the translational capacity of the identified translons, we engineer a translon-dependent GFP reporter system and detect expression of translons initiating at ATG and near-cognate start codons in mouse embryonic stem cells (mESCs). We identify distinct expression patterns of translons using a comparative analysis of more than a thousand ribosome profiling datasets across a wide range of cell types. Further, using a machine learning model, we predict that specific upstream translons in synaptically enriched mRNAs regulate translation efficiency of the annotated coding region. Taken together, we present a proof-of-concept study to identify non-canonical translation events from low input samples which can be applied to cell and tissue types inaccessible to conventional methods.
    DOI:  https://doi.org/10.1038/s41467-026-75571-y
  7. Methods Mol Biol. 2026 ;3047 203-223
    Fluorescence-Based mRNA Translation Reporter.
    Jemima Riess, Gunhild Sommer, Tilman Heise.
      Herein, we describe a fluorescence reporter assay for investigating regulatory elements in the 5'-UTR of mRNA that modulate translational initiation. The canonical translation initiation process generally begins with the assembly of the eIF4F complex at the cap structure, the formation of the ternary complex, which is loaded with the initiator tRNA, and finally, the preinitiation complex. The preinitiation complex then scans the 5'-UTR to identify the authentic translation start site, which is typically characterized by an AUG codon within a sequence context known as the Kozak sequence. It is well established that the 5'-UTR varies extensively in length and contains regulatory, structural, and sequence elements. To investigate these elements, we use a green fluorescence protein (GFP)- and a luciferase-based mRNA reporter. These reporters can be quickly generated by ordering gBlocks or by PCR-based template generation for in vitro transcription, capping and polyadenylation, to produce synthetic mRNAs. These mRNAs can be transfected into cells, and expression can be monitored via GFP fluorescence or by measuring luciferase activity. In this chapter, we provide a step-by-step protocol for designing gBlocks, generating the reporter mRNA, transfecting the cells, and analyzing the results.
    Keywords:  5′-untranslated region; Cell-based assay; Fluorescence; Luciferase; RNA structure; RNA-binding; RNA-binding protein; Reporter; Translation
    DOI:  https://doi.org/10.1007/978-1-0716-5352-4_16
  8. Nat Commun. 2026 08 03. pii: 9320. [Epub ahead of print]17(1):
    Unbiased screen of human transcriptome reveals an unexpected role of 3'UTRs in translation initiation.
    Yun Yang, Xiaojuan Fan, Yanwen Ye, Zhenzhen Zhang, Chuyun Chen, Sebastian E J Ludwig, Sirui Zhang, Qianyun Lu, Cindy L Will, Henning Urlaub, Jing Sun, Reinhard Lührmann, Zefeng Wang.
      Although most eukaryotic mRNAs require a 5'-cap for translation initiation, some can also be translated through a poorly studied cap-independent pathway. Here we develop a circRNA-based system and unbiasedly identify more than 10,000 sequences in the human transcriptome that contain Cap-independent Translation Initiators (CiTIs). Surprisingly, most of the identified CiTIs are located in 3'UTRs, which mainly promote translation initiation in mRNAs bearing highly structured 5'UTR. Mechanistically, CiTI recruits several translation initiation factors including eIF3 and DHX29, which in turn unwind 5'UTR structures and facilitate ribosome scanning. Functionally, we show that the translation of HIF1A mRNA, an endogenous DHX29 target, is antagonistically regulated by its 5'UTR structure and a new 3'-CiTI in response to hypoxia. Consistently, deletion of 3'-CiTI suppresses cell growth in hypoxia and tumor progression in vivo. Collectively, our study uncovers a new regulatory mode for translation where the 3'UTR actively participate in the translation initiation.
    DOI:  https://doi.org/10.1038/s41467-026-75574-9
  9. FEBS Open Bio. 2026 Aug 31.
    Genetic dissection of human ABCE1 in yeast reveals separable requirements for ribosome recycling and suppression of aberrant reinitiation.
    Eriko Nakata, Yuxin Li, Kei Endo, Koichi Ito.
      The ATP-binding cassette E1 (ABCE1) protein is an essential factor for ribosome recycling, splitting post-termination ribosomes into subunits for subsequent rounds of translation. Despite high conservation, human ABCE1 (hABCE1) fails to functionally complement the depletion of its essential yeast homolog, Rli1. In this study, we leveraged this species-specificity to dissect the functional architecture of ABCE1. Through analysis of yeast-human chimeric proteins, we identified the N-terminal nucleotide-binding domain (NBD1) as the primary determinant of this incompatibility. To further investigate, we isolated multiple hABCE1 point mutants (revertants) that successfully restored yeast growth. We then developed a novel dual-luciferase reporter assay to quantify aberrant translation reinitiation in the 3'UTR, an event recognized as a direct consequence of ABCE1 deficiency. Notably, while the revertant mutants rescued yeast viability, they failed to suppress aberrant reinitiation, exhibiting levels equivalent to the nonfunctional hABCE1. This genetic uncoupling of viability from the suppression of reinitiation suggests that the canonical ribosome recycling function required for cell growth and the role in preventing aberrant reinitiation have distinct functional thresholds or are genetically separable aspects of ABCE1 activity.
    Keywords:  ABCE1; Rli1; Saccharomyces cerevisiae; ribosome recycling; species‐specificity; translational integrity
    DOI:  https://doi.org/10.1002/2211-5463.70337
  10. Cell Rep. 2026 Aug 28. pii: S2211-1247(26)00892-2. [Epub ahead of print]45(9): 117814
    An Epstein-Barr virus-encoded snoRNA directs 2'-O-methylation of human rRNAs to control translation and the viral lytic switch.
    Yarden Dan, Beáta E Jády, Yudit Halperin, Yuval Nevo, Aliza Fedorenko, Anat Bashan, Maram Arafat, Pnina Glick, Ada Yonath, Tamás Kiss, Daphna Nachmani.
      Epstein-Barr virus (EBV) establishes life-long latency in human B cells yet the molecular strategies that balance its persistence with lytic replication remain incompletely understood. Here, we identify the EBV-encoded small nucleolar RNA, v-snoRNA1, as a bona fide 2'-O-methylation guide that directs methylation of host ribosomal RNAs at 18S-C621 and 28S-U1760, two conserved residues in the ribosomal A-site. V-snoRNA1-mediated hypermethylation impairs 18S rRNA maturation and compromises translational fidelity and output, resulting in slower cellular proliferation. Infection with a v-snoRNA1 deleted virus (Δv-snoRNA1) leads to enhanced protein synthesis and increased proliferation, together with extensive rewiring of host and viral gene expression. This rewiring includes suppression of immune and interferon pathways and alterations in transcription factor activities important for B cell differentiation. Importantly, we find that v-snoRNA1 is required to facilitate viral production. Our findings reveal a molecular strategy by which EBV directly controls translation to promote infection.
    Keywords:  2′-O-methylation; CP: immunology; CP: molecular biology; EBV; rRNA; ribosome; snoRNA; translation
    DOI:  https://doi.org/10.1016/j.celrep.2026.117814
  11. Methods Mol Biol. 2026 ;3047 109-116
    RNA Labeling of Nucleolar Transcripts by 5-Ethynyl Uridine Click Chemistry.
    Juyeon Lee, Kyung-Ha Lee.
      The nucleolus is a dynamic membraneless organelle where ribosomal RNA (rRNA) transcription, processing, and ribonucleoprotein assembly occur. Visualizing nascent RNA within nucleolar condensates reveals how RNA metabolism and phase separation reorganize under stress. This chapter provides a practical protocol to label nascent RNA using 5-ethynyl uridine (5-EU), followed by copper-catalyzed azide-alkyne cycloaddition for fluorescent detection. The method is straightforward, works across mammalian cells, and robustly reports nucleolar transcription under basal and stress conditions (heat shock; low-dose actinomycin D). Step-by-step instructions, reagent setup, image analysis metrics, troubleshooting, safety, and expected results are included so that researchers can reproducibly implement the assay.
    Keywords:  5-ethynyl uridine; Actinomycin D; Click chemistry; Condensates; Heat shock; Nascent RNA; Nucleolar stress; Nucleolus; RNA labeling
    DOI:  https://doi.org/10.1007/978-1-0716-5352-4_9
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