{"doi":"10.1093/nar/gkaf794","title":"Sm-site containing mRNAs can accept Sm-rings and are downregulated in Spinal Muscular Atrophy","abstract":"Sm-ring assembly is important for the biogenesis, stability, and function of uridine-rich small nuclear RNAs (U snRNAs) involved in pre-messenger RNA (mRNA) splicing and histone pre-mRNA processing. Sm-ring assembly is cytoplasmic and dependent upon the Sm-site sequence and structural motif, ATP, and Survival motor neuron (SMN) protein complex. While RNAs other than U snRNAs were previously shown to associate with Sm proteins, whether this association follows Sm-ring assembly requirements is unknown. We systematically identified Sm-sites within the human and mouse transcriptomes and assessed whether these sites can accept Sm-rings. In addition to snRNAs, Sm-sites are highly prevalent in the 3' untranslated regions of long mRNAs. RNA immunoprecipitation experiments confirm that Sm-site containing mRNAs associate with Sm proteins in the cytoplasm. In modified Sm-ring assembly assays, Sm-site containing mRNAs, specifically associate with Sm proteins in an Sm-site, SMN, and ATP-dependent manner. In cell and animal models of Spinal Muscular Atrophy (SMA), mRNAs containing Sm-sites are downregulated, suggesting reduced Sm-ring assembly on these mRNAs may contribute to SMA pathogenesis. Together, this study establishes that Sm-site containing mRNAs can accept Sm-rings and identifies a novel mechanism for Sm proteins in regulation of cytoplasmic mRNAs.","journal":"Nucleic Acids Research","year":2025,"id":572671,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"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":276663,"name":"Manu Sanjeev","orcid":null,"position":1,"is_corresponding":false},{"id":988890,"name":"Jacob A. Slivka","orcid":null,"position":2,"is_corresponding":false},{"id":666003,"name":"Benjamin Pastore","orcid":"0000-0001-9278-222X","position":3,"is_corresponding":false},{"id":868915,"name":"Caleb M. Embree","orcid":"0000-0002-7437-4510","position":4,"is_corresponding":false},{"id":553445,"name":"Wen Tang","orcid":"0000-0001-6684-5258","position":5,"is_corresponding":false},{"id":275564,"name":"Guramrit Singh","orcid":"0000-0002-5283-9540","position":6,"is_corresponding":false},{"id":703526,"name":"Arthur H.M. Burghes","orcid":"0000-0001-9031-1555","position":7,"is_corresponding":false},{"id":713258,"name":"Anton J. Blatnik","orcid":"0000-0002-3557-9011","position":0,"is_corresponding":true}],"reference_count":141,"raw_metadata":null,"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40823813","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":[]}