{"doi":"10.1016/j.cell.2021.03.062","title":"Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA splicing","abstract":"The N 6 -methyladenosine (m 6 A) RNA modification is used widely to alter the fate of mRNAs. Here we demonstrate that the C. elegans writer METT-10 (the ortholog of mouse METTL16) deposits an m 6 A mark on the 3′ splice site (AG) of the S-adenosylmethionine (SAM) synthetase pre-mRNA, which inhibits its proper splicing and protein production. The mechanism is triggered by a rich diet and acts as an m 6 A-mediated switch to stop SAM production and regulate its homeostasis. Although the mammalian SAM synthetase pre-mRNA is not regulated via this mechanism, we show that splicing inhibition by 3′ splice site m 6 A is conserved in mammals. The modification functions by physically preventing the essential splicing factor U2AF35 from recognizing the 3′ splice site. We propose that use of splice-site m 6 A is an ancient mechanism for splicing regulation.","journal":"Cell","year":2021,"id":146344,"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":231,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":621750,"name":"Kamila Delaney","orcid":"0000-0002-1006-9146","position":1,"is_corresponding":false},{"id":551670,"name":"Radha Raman Pandey","orcid":"0000-0002-4439-8386","position":2,"is_corresponding":false},{"id":621751,"name":"Kuan‐Ming Chen","orcid":"0000-0003-1715-5319","position":3,"is_corresponding":false},{"id":555800,"name":"Joanna M. Wenda","orcid":"0000-0002-7312-6777","position":4,"is_corresponding":false},{"id":621752,"name":"Cathrine Broberg Vågbø","orcid":"0000-0003-3959-7409","position":5,"is_corresponding":false},{"id":621753,"name":"Florian Steiner","orcid":"0000-0002-0514-5060","position":6,"is_corresponding":false},{"id":551671,"name":"David Homolka","orcid":"0000-0002-6662-3409","position":7,"is_corresponding":false},{"id":551672,"name":"Ramesh S. Pillai","orcid":"0000-0003-2080-3604","position":8,"is_corresponding":false},{"id":622600,"name":"Mateusz Mendel","orcid":null,"position":0,"is_corresponding":true}],"reference_count":110,"raw_metadata":null,"created_at":"2026-07-18T23:42:18.947086Z","pmid":"33930289","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":[]}