{"doi":"10.1093/nar/gkad773","title":"Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery","abstract":"Translational readthrough of UGA stop codons by selenocysteine-specific tRNA (tRNASec) enables the synthesis of selenoproteins. Seryl-tRNA synthetase (SerRS) charges tRNASec with serine, which is modified into selenocysteine and delivered to the ribosome by a designated elongation factor (eEFSec in eukaryotes). Here we found that components of the human selenocysteine incorporation machinery (SerRS, tRNASec, and eEFSec) also increased translational readthrough of non-selenocysteine genes, including VEGFA, to create C-terminally extended isoforms. SerRS recognizes target mRNAs through a stem-loop structure that resembles the variable loop of its cognate tRNAs. This function of SerRS depends on both its enzymatic activity and a vertebrate-specific domain. Through eCLIP-seq, we identified additional SerRS-interacting mRNAs as potential readthrough genes. Moreover, SerRS overexpression was sufficient to reverse premature termination caused by a pathogenic nonsense mutation. Our findings expand the repertoire of selenoprotein biosynthesis machinery and suggest an avenue for therapeutic targeting of nonsense mutations using endogenous factors.","journal":"Nucleic Acids Research","year":2023,"id":338825,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":469465,"name":"Justin Wang","orcid":"0009-0000-4224-9443","position":1,"is_corresponding":false},{"id":484863,"name":"Yi Shi","orcid":"0000-0003-2530-410X","position":2,"is_corresponding":false},{"id":43217,"name":"Brian A. Yee","orcid":"0000-0001-5615-8550","position":3,"is_corresponding":false},{"id":824210,"name":"Markus Terrey","orcid":"0000-0002-7359-4810","position":4,"is_corresponding":false},{"id":636310,"name":"Qian Zhang","orcid":"0000-0003-1188-8335","position":5,"is_corresponding":false},{"id":1072387,"name":"Jenq‐Chang Lee","orcid":null,"position":6,"is_corresponding":false},{"id":1054327,"name":"Kuo‐I Lin","orcid":"0000-0003-4477-0798","position":7,"is_corresponding":false},{"id":1071785,"name":"Andrew H.‐J. Wang","orcid":"0000-0002-0016-5337","position":8,"is_corresponding":false},{"id":300751,"name":"Susan L. Ackerman","orcid":"0000-0002-6740-593X","position":9,"is_corresponding":false},{"id":43290,"name":"G Yeo","orcid":null,"position":10,"is_corresponding":false},{"id":335118,"name":"Haissi Cui","orcid":"0000-0003-3358-8958","position":11,"is_corresponding":false},{"id":479459,"name":"Xiang‐Lei Yang","orcid":"0000-0003-2554-084X","position":12,"is_corresponding":false},{"id":416193,"name":"Ze Liu","orcid":"0000-0002-1635-5573","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:10:40.496978Z","pmid":"37739431","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":[]}