{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zheng Z"],"funding":["Research Grants Council, University Grants Committee","Research Grants Council, University Grants Committee (RGC, UGC)"],"pagination":["6718"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12280072"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["How the ubiquitously expressed splicing factors specifically regulate neural crest (NC) development and enhance their vulnerability to splicing perturbations remain poorly understood. Here, we show that NC-specific DLC1, partnering with SF3B1-PHF5A splicing complex, are crucial for determining avian trunk NC cell fate by regulating the splicing of NC specifiers SOX9 and SNAI2 pre-mRNAs rather than their upstream regulators BMP4, WNT1, and PAX7. Mechanistically, SF3B1-PHF5A binds to the intronic branch site (BS) sequences of all factors, while DLC1 interacts with a specific motif near the BS sequences of SOX9 and SNAI2, thereby determining their functional specificity in NC specification. Moreover, DLC1 increases NC cells' vulnerability to splicing modulator pladienolide B (PB) by reducing "],"journal":["Nature communications"],"pubmed_title":["Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex."],"pmcid":["PMC12280072"],"funding_grant_id":["17101622","17102420"],"pubmed_authors":["Zheng Z","Tam HY","Cheung MPL","Wong KKW","Liu JA","Sharma R","Rao Y","Hui MN","Guo S","Leung AWL","Wang J","Cheung M"],"additional_accession":[]},"is_claimable":false,"name":"Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex.","description":"How the ubiquitously expressed splicing factors specifically regulate neural crest (NC) development and enhance their vulnerability to splicing perturbations remain poorly understood. Here, we show that NC-specific DLC1, partnering with SF3B1-PHF5A splicing complex, are crucial for determining avian trunk NC cell fate by regulating the splicing of NC specifiers SOX9 and SNAI2 pre-mRNAs rather than their upstream regulators BMP4, WNT1, and PAX7. Mechanistically, SF3B1-PHF5A binds to the intronic branch site (BS) sequences of all factors, while DLC1 interacts with a specific motif near the BS sequences of SOX9 and SNAI2, thereby determining their functional specificity in NC specification. Moreover, DLC1 increases NC cells' vulnerability to splicing modulator pladienolide B (PB) by reducing ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-03-31T10:42:35.574Z","creation":"2025-08-24T03:08:47.559Z"},"accession":"S-EPMC12280072","cross_references":{"pubmed":["40691464"],"doi":["10.1038/s41467-025-62003-6"]}}