{"doi":"10.1093/nar/gkae447","title":"U6 snRNA m6A modification is required for accurate and efficient splicing of <i>C. elegans</i> and human pre-mRNAs","abstract":"pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that the conserved U6 snRNA m6A methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of METT-10 in C. elegans and METTL16 in humans primarily leads to alternative splicing at 5' splice sites with an adenosine at +4 position. In addition, METT-10 is required for splicing of weak 3' cis- and trans-splice sites. We identified a significant overlap between METT-10 and the conserved splicing factor SNRNP27K in regulating 5' splice sites with +4A. Finally, we show that editing endogenous 5' splice site +4A positions to +4U restores splicing to wild-type positions in a mett-10 mutant background, supporting a direct role for U6 snRNA m6A modification in 5' splice site recognition. We conclude that the U6 snRNA m6A modification is important for accurate and efficient pre-mRNA splicing.","journal":"Nucleic Acids Research","year":2024,"id":430411,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1170401,"name":"Katarzyna Hencel","orcid":null,"position":1,"is_corresponding":false},{"id":33798,"name":"Matthew T. Parker","orcid":"0000-0002-0891-8495","position":2,"is_corresponding":false},{"id":894145,"name":"Robyn Scott","orcid":"0000-0001-6450-4708","position":3,"is_corresponding":false},{"id":1170402,"name":"Roberta Skukan","orcid":null,"position":4,"is_corresponding":false},{"id":1169904,"name":"Aduragbemi S. Adesina","orcid":"0000-0002-1029-4159","position":5,"is_corresponding":false},{"id":1169905,"name":"Carey L. Metheringham","orcid":"0000-0002-5295-694X","position":6,"is_corresponding":false},{"id":304354,"name":"Eric A. Miska","orcid":"0000-0002-4450-576X","position":7,"is_corresponding":false},{"id":30048,"name":"Yunsun Nam","orcid":"0000-0002-7939-8626","position":8,"is_corresponding":false},{"id":88700,"name":"Wilfried Haerty","orcid":"0000-0003-0111-191X","position":9,"is_corresponding":false},{"id":7298,"name":"Gordon G. Simpson","orcid":"0000-0001-6744-5889","position":10,"is_corresponding":false},{"id":489048,"name":"Alper Akay","orcid":"0000-0001-6825-4443","position":11,"is_corresponding":false},{"id":1170400,"name":"Aykut Shen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-19T01:59:16.092672Z","pmid":"38808663","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":[]}