{"doi":"10.1101/gad.1422106","title":"RS domains contact splicing signals and promote splicing by a common mechanism in yeast through humans","abstract":"\n Serine–arginine (SR) proteins are general metazoan splicing factors that contain an essential arginine–serine-rich (RS) domain. We have previously found that mammalian spliceosome assembly involves a series of sequential interactions between RS domains and two splicing signals: the branchpoint and the 5′ splice site. Here we study how RS domains are directed to specifically contact splicing signals, and how this interaction promotes splicing. The yeast\n Saccharomyces cerevisiae\n lacks SR proteins. However, we show that tethering a mammalian RS domain to a yeast actin pre-mRNA rescues splicing of certain branchpoint or 5′ splice site mutants in which U snRNA base-pairing has been decreased. Conversely, on a mammalian pre-mRNA, a normally essential SR protein becomes dispensable when the complementarity of a splicing signal to a U snRNA is increased. We find that in the absence of other splicing factors an RS domain tethered to a pre-mRNA selectively contacts a double-stranded RNA region and enhances RNA–RNA base-pairing. Significantly, all of these activities require phosphorylation of the RS domain. Based on these results, we propose that RS domains selectively contact splicing signals because, due to transient U snRNA base-pairing, they are partially double-stranded. The RS domain–splicing signal interaction, in turn, promotes (or stabilizes) base-pairing between the U snRNA and pre-mRNA substrate, thereby enhancing splicing. Our results reveal a common mechanism of RS domain function in yeast through humans.\n ","journal":"Genes & Development","year":2006,"id":34282,"datarank":5.977227885186578,"base_score":5.049856007249537,"endowment":5.049856007249537,"self_citation_contribution":0.7574784010874307,"citation_network_contribution":5.219749484099148,"self_endowment_contribution":0.7574784010874307,"citer_contribution":5.219749484099148,"corpus_percentile":null,"corpus_rank":null,"citation_count":155,"citer_count":149,"citers_with_citation_signal":117,"citers_with_endowment":117,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":17225,"name":"Michael R. Green","orcid":"0000-0001-6309-9472","position":1,"is_corresponding":false},{"id":169688,"name":"Haihong Shen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.049856007249537,"endowment":5.049856007249537,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16766678","pmcid":"PMC1522072","openalex_id":"https://openalex.org/W2021033136","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM035490","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":2,"citation_trend":[{"year":2012,"count":11},{"year":2013,"count":8},{"year":2014,"count":7},{"year":2015,"count":8},{"year":2016,"count":3},{"year":2017,"count":5},{"year":2018,"count":3},{"year":2019,"count":8},{"year":2020,"count":5},{"year":2021,"count":8},{"year":2022,"count":4},{"year":2023,"count":1},{"year":2024,"count":11},{"year":2025,"count":2}],"oa_status":"gold","license":null,"oa_locations":[{"url":"http://genesdev.cshlp.org/content/20/13/1755.full.pdf","host_type":"journal"},{"url":"http://genesdev.cshlp.org/content/20/13/1755.full.pdf","host_type":"GOLD"},{"url":"http://genesdev.cshlp.org/content/20/13/1755.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gad.1422106","host_type":"publisher"},{"url":"https://doi.org/10.1101/gad.1422106","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16766678","host_type":"repository"},{"url":"https://escholarship.umassmed.edu/oapubs/572","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1522072","host_type":"repository"}],"fields_of_study":["RNA Research and Splicing","RNA modifications and cancer","RNA and protein synthesis mechanisms","Medicine","Biology","Arginine","Base Pairing","Evolution, Molecular","Humans","Mutation","Phosphorylation","Protein Serine-Threonine Kinases","Protein Structure, Tertiary","RNA Precursors","RNA Splicing","RNA, Double-Stranded","RNA, Fungal","RNA, Small Nuclear","Ribonucleoproteins, Small Nuclear","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins","Serine","Spliceosomes"],"mesh_terms":["Arginine","Humans","Mutation","Phosphorylation","RNA Precursors","RNA Splicing","RNA, Double-Stranded","RNA, Fungal","RNA, Small Nuclear","Saccharomyces cerevisiae","Serine","Protein Serine-Threonine Kinases","Spliceosomes","Ribonucleoproteins, Small Nuclear","Protein Structure, Tertiary","Evolution, Molecular","Base Pairing","Saccharomyces cerevisiae Proteins"],"keywords":["Prp24","RNA splicing","Biology","snRNP","SR protein","Small nuclear RNA","Exonic splicing enhancer","Protein splicing","Splicing factor","Cell biology","Spliceosome","RNA-binding protein","Genetics","Alternative splicing","RNA","Messenger RNA","Non-coding RNA","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T18:10:24.404992Z","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":[]}