{"doi":"10.1126/sciadv.ady4521","title":"Serine tRNAs compete to regulate the mRNA translation of serine-sensitive codons","abstract":"Differential mRNA translation efficiency (mTE) of codons is important in regulating protein synthesis and cellular states and can change in response to amino acid availability. While the mTE of codons is canonically associated with their corresponding transfer RNA (tRNA) isoacceptors, its regulation by amino acids in mammalian cells remains unexplored. We found that ELAC2, a 3′ tRNA maturation endonuclease, decreases the mTE of UC[C/U] serine (Ser) codons in response to Ser limitation. Ablation of ELAC2 restored UC[C/U] mTE but reduced the mTE of AG[U/C] Ser codons. Among the tRNA Ser isoacceptors, tRNA Ser(GCU) decreased the most in ELAC2 -deficient cells. Unexpectedly, tRNA Ser(GCU) delivery restored AG[U/C] mTE and reduced UC[C/U] mTE in ELAC2 -deficient cells. Last, we deciphered the effects of Ser-sensitive codons on mRNA translation and the human proteome. Our study revealed that in response to Ser limitation, regulation of tRNA Ser(GCU) levels fine-tune the mTE of UC[C/U] or AG[U/C] Ser-sensitive codons and shapes the proteome.","journal":"Science Advances","year":2025,"id":548534,"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":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1382847,"name":"Wyatt C. Tran","orcid":"0009-0002-6162-6261","position":1,"is_corresponding":false},{"id":1441728,"name":"Nandhini Rajesh Babu","orcid":"0009-0008-7676-8805","position":2,"is_corresponding":false},{"id":262458,"name":"Evgeny Kanshin","orcid":"0000-0001-7142-4554","position":3,"is_corresponding":false},{"id":231337,"name":"Beatrix Ueberheide","orcid":"0000-0003-2512-0204","position":4,"is_corresponding":false},{"id":103967,"name":"Alec C. Kimmelman","orcid":"0009-0002-9465-8411","position":5,"is_corresponding":false},{"id":237051,"name":"Robert S. Banh","orcid":"0000-0003-1959-4622","position":6,"is_corresponding":false},{"id":426393,"name":"Veronica Costiniti","orcid":"0000-0002-8472-7797","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:53:58.530220Z","pmid":"41237252","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":[]}