{"doi":"10.1101/2022.05.14.491930","title":"tRNA Methylation Resolves Codon Usage Bias at the Limit of Cell Viability","abstract":"Summary The codon usage of each genome is closely correlated with the abundance of tRNA isoacceptors. How codon-usage bias is resolved by tRNA post-transcriptional modifications is largely unknown. Here we demonstrate that the N 1 -methylation of guanosine at position 37 (m 1 G37) on the 3’-side of the anticodon, while not directly responsible for reading of codons, is a neutralizer that resolves differential decoding of proline codons. A genome-wide suppressor screen of a non-viable E. coli strain, m 1 G37-lacking, identifies proS suppressor mutations, indicating a coupling of methylation with tRNA prolyl-aminoacylation that sets the limit of cell viability. Using these suppressors, where prolyl-aminoacylation is decoupled from tRNA methylation, we show that m 1 G37 neutralizes differential translation of proline codons by the major isoacceptor. Lacking of m 1 G37 inactivates this neutralization and exposes the need for a minor isoacceptor for cell viability. This work has medical implications for bacterial genomes that exclusively use the major isoacceptor for survival.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303297,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":898228,"name":"Yuka Yamaki","orcid":"0000-0003-2457-7296","position":1,"is_corresponding":false},{"id":898229,"name":"Rajesh Detroja","orcid":"0000-0003-2617-6998","position":2,"is_corresponding":false},{"id":470189,"name":"Somnath Tagore","orcid":"0000-0001-9603-1263","position":3,"is_corresponding":false},{"id":898230,"name":"Henry Moore","orcid":"0000-0001-5822-0282","position":4,"is_corresponding":false},{"id":451352,"name":"Sunita Maharjan","orcid":"0000-0002-7099-1802","position":5,"is_corresponding":false},{"id":898231,"name":"Yuko Nakano","orcid":"0000-0001-7583-004X","position":6,"is_corresponding":false},{"id":671484,"name":"Thomas Christian","orcid":null,"position":7,"is_corresponding":false},{"id":749697,"name":"Ryuma Matsubara","orcid":"0000-0001-7989-4104","position":8,"is_corresponding":false},{"id":19953,"name":"Todd M. Lowe","orcid":"0000-0003-3253-6021","position":9,"is_corresponding":false},{"id":14359,"name":"Milana Frenkel‐Morgenstern","orcid":"0000-0002-0329-4599","position":10,"is_corresponding":false},{"id":17829,"name":"Ya-Ming Hou","orcid":"0000-0001-6546-2597","position":11,"is_corresponding":false},{"id":396902,"name":"Isao Masuda","orcid":"0000-0001-9385-4424","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","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":[]}