{"doi":"10.1073/pnas.2401154121","title":"Modifications in the T arm of tRNA globally determine tRNA maturation, function, and cellular fitness","abstract":"<jats:p>\n                    Almost all elongator tRNAs (Transfer RNAs) harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, generated by the enzymes TrmA and TruB, respectively, in\n                    <jats:italic>Escherichia coli.</jats:italic>\n                    TrmA and TruB both act as tRNA chaperones, and strains lacking\n                    <jats:italic>trmA</jats:italic>\n                    or\n                    <jats:italic>truB</jats:italic>\n                    are outcompeted by wild type. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>truB</jats:italic>\n                    in\n                    <jats:italic>E. coli</jats:italic>\n                    causes a global decrease in aminoacylation and alters other tRNA modifications such as acp\n                    <jats:sup>3</jats:sup>\n                    U47. While overall protein synthesis is not affected in\n                    <jats:italic>Δ</jats:italic>\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>Δ</jats:italic>\n                    <jats:italic>truB</jats:italic>\n                    strains, the translation of a subset of codons is significantly impaired. As a consequence, we observe translationally reduced expression of many specific proteins, that are either encoded with a high frequency of these codons or that are large proteins. The resulting proteome changes are not related to a specific growth phenotype, but overall cellular fitness is impaired upon deleting\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>truB</jats:italic>\n                    in accordance with a general protein synthesis impact. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness irrespective of the growth conditions which explains the conservation of\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>truB</jats:italic>\n                    .\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":650778,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284941,"name":"Christopher D. Katanski","orcid":"0000-0002-1707-081X","position":1,"is_corresponding":false},{"id":1696938,"name":"Mateusz Halucha","orcid":null,"position":2,"is_corresponding":false},{"id":922979,"name":"Noah Peña","orcid":"0000-0002-9079-4638","position":3,"is_corresponding":false},{"id":1254880,"name":"Richard P. Fahlman","orcid":"0000-0003-4104-6374","position":4,"is_corresponding":false},{"id":371532,"name":"Tao Pan","orcid":"0000-0003-1096-8405","position":5,"is_corresponding":false},{"id":833129,"name":"Ute Kothe","orcid":"0000-0002-2744-7334","position":6,"is_corresponding":false},{"id":833128,"name":"Sarah K. Schultz","orcid":"0000-0001-8425-1840","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Modifications in the T arm of tRNA globally determine tRNA maturation, function, and cellular fitness","abstract":"<jats:p>\n                    Almost all elongator tRNAs (Transfer RNAs) harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, generated by the enzymes TrmA and TruB, respectively, in\n                    <jats:italic>Escherichia coli.</jats:italic>\n                    TrmA and TruB both act as tRNA chaperones, and strains lacking\n                    <jats:italic>trmA</jats:italic>\n                    or\n                    <jats:italic>truB</jats:italic>\n                    are outcompeted by wild type. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>truB</jats:italic>\n                    in\n                    <jats:italic>E. coli</jats:italic>\n                    causes a global decrease in aminoacylation and alters other tRNA modifications such as acp\n                    <jats:sup>3</jats:sup>\n                    U47. While overall protein synthesis is not affected in\n                    <jats:italic>Δ</jats:italic>\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>Δ</jats:italic>\n                    <jats:italic>truB</jats:italic>\n                    strains, the translation of a subset of codons is significantly impaired. As a consequence, we observe translationally reduced expression of many specific proteins, that are either encoded with a high frequency of these codons or that are large proteins. The resulting proteome changes are not related to a specific growth phenotype, but overall cellular fitness is impaired upon deleting\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>truB</jats:italic>\n                    in accordance with a general protein synthesis impact. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness irrespective of the growth conditions which explains the conservation of\n                    <jats:italic>trmA</jats:italic>\n                    and\n                    <jats:italic>truB</jats:italic>\n                    .\n                  </jats:p>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38889150","pmcid":"PMC11214086","openalex_id":"https://openalex.org/W4399770366","authors":[],"funders":[{"funder_name":"Canadian Government | Natural Sciences and Engineering Research Council of Canada","grant_id":"RGPIN-2020-04965","title":null},{"funder_name":"Canadian Government | Natural Sciences and Engineering Research Council of Canada","grant_id":"RGPAS-2020-00010","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R25 GM109439","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"}],"total_grants":4,"fwci":5.7557,"citation_percentile":0.97281492,"influential_citations":0,"citation_trend":[{"year":2024,"count":6},{"year":2025,"count":16},{"year":2026,"count":14}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.2401154121","host_type":"journal"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.2401154121","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2401154121","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.2401154121","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38889150","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11214086","host_type":"repository"},{"url":"http://knowledge.uchicago.edu/record/12677","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11214086/pdf/pnas.202401154.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11214086","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11214086?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2023.11.11.566336","host_type":""},{"url":"https://dx.doi.org/10.6082/pz8se-pzb72","host_type":""},{"url":"https://dx.doi.org/10.6082/xef2h-q7414","host_type":""},{"url":"http://dx.doi.org/10.1073/pnas.2401154121","host_type":""},{"url":"https://doi.org/https://doi.org/10.1073/pnas.2401154121","host_type":""}],"fields_of_study":["RNA modifications and cancer","RNA and protein synthesis mechanisms","Genomics and Phylogenetic Studies","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Escherichia coli","RNA Processing, Post-Transcriptional","RNA, Transfer","tRNA Methyltransferases","Protein Biosynthesis","Escherichia coli Proteins"],"keywords":["Transfer RNA","Biology","Aminoacylation","Translation (biology)","Protein biosynthesis","Function (biology)","Phenotype","Genetics","RNA","Biochemistry","Gene","Messenger RNA","Methylation","Protein synthesis","Pseudouridine","Trna Modification","tRNA Methyltransferases","Escherichia coli Proteins","Biological Sciences","RNA, Transfer","Escherichia coli","RNA Processing, Post-Transcriptional"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T06:05:35.623018Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}