{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu J"],"funding":["Germany's Excellence Strategy","German Research Foundation","Swiss National Science Foundation","SFB 1381","European Research Council","Polish Ministry and Higher Education","Marie Sklodowska-Curie Postdoctoral Fellowship","European Union","PLGrid","Dutch Research Council (NWO)","European Commission"],"pagination":["gkaf1311"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12721868"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["53(22)"],"pubmed_abstract":["Transfer RNA (tRNA) modifications tune translation rates and codon optimality, thereby optimizing co-translational protein folding. However, the mechanisms by which tRNA modifications modulate codon optimality and trigger phenotypes remain unclear. Here, we show that ribosomes stall at specific modification-dependent codon pairs in wobble uridine modification (U34) mutants. This triggers ribosome collisions and a coordinated hierarchical response of cellular quality control pathways. High-resolution ribosome profiling reveals an unexpected functional diversity of U34 modifications during decoding. For instance, 5-carbamoylmethyluridine (ncm5U) exhibits distinct effects at the A and P sites. Importantly, ribosomes only slow down at a fraction of codons decoded by hypomodified tRNA, and the "],"journal":["Nucleic acids research"],"pubmed_title":["Suboptimal codon pairs trigger ribosome collisions and cellular quality control responses in tRNA modification mutants."],"pmcid":["PMC12721868"],"funding_grant_id":["219536","669168","746340","409673687","101001394","403222702","1/SOL/2021/2","019.162LW.028","769065","390939984","PLG/2020/014009","259130777"],"pubmed_authors":["Wu J","Sin O","Fufezan C","Leidel SA","Mancilla H","Kraft C","Scholer HR","Mollet F","Drexler HCA","Ranff T","Koziej L","Glatt S","Bruder JM","Eggers C"],"additional_accession":[]},"is_claimable":false,"name":"Suboptimal codon pairs trigger ribosome collisions and cellular quality control responses in tRNA modification mutants.","description":"Transfer RNA (tRNA) modifications tune translation rates and codon optimality, thereby optimizing co-translational protein folding. However, the mechanisms by which tRNA modifications modulate codon optimality and trigger phenotypes remain unclear. Here, we show that ribosomes stall at specific modification-dependent codon pairs in wobble uridine modification (U34) mutants. This triggers ribosome collisions and a coordinated hierarchical response of cellular quality control pathways. High-resolution ribosome profiling reveals an unexpected functional diversity of U34 modifications during decoding. For instance, 5-carbamoylmethyluridine (ncm5U) exhibits distinct effects at the A and P sites. Importantly, ribosomes only slow down at a fraction of codons decoded by hypomodified tRNA, and the ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-04T03:18:19.114Z","creation":"2026-06-04T03:12:18.022Z"},"accession":"S-EPMC12721868","cross_references":{"pubmed":["41429421"],"doi":["10.1093/nar/gkaf1311"]}}