PXD064804

PXD064804 is an original dataset announced via ProteomeXchange.

Title	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 by reducing the binding capacity of the SF3B1-PHF5A splicing complex to the shorter length of both SOX9 intron 2 and SNAI2 intron 1, which possess weaker polypyrimidine tract 3’ of the BS sequence, resulting in intron retention and loss of NC progenitors. Conversely, somite specific SLU7-SF3B1-PHF5A splicing complex regulates SOX9 and SNAI2 expression and imparts resistance to PB. Our data reveal the cell-type specific splicing complexes with distinct vulnerabilities to PB, highlighting the critical role of the DLC1-SF3B1-PHF5A in determining trunk NC cell fate and enhancing its susceptibility to splicing perturbation.
HostingRepository	iProX
AnnounceDate	2025-06-09
AnnouncementXML	Submission_2025-08-05_21:37:02.363.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhengfan Zheng
SpeciesList	scientific name: Gallus gallus; NCBI TaxID: 9031;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-09 23:41:46	ID requested
1	2025-06-09 23:42:00	announced
⏵ 2	2025-08-05 21:37:03	announced	2025-08-06: Add info.

Zheng Z, Guo S, Tam HY, Wang J, Rao Y, Hui MN, Cheung MPL, Leung AWL, Wong KKW, Sharma R, Liu JA, Cheung M, Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex. Nat Commun, 16(1):6718(2025) [pubmed]

submitter keyword: Neural crest development, Splicing factors

Martin Cheung
contact affiliation	University of Hong Kong
contact email	mcheung9@hku.hk
lab head
Zhengfan Zheng
contact affiliation	The University of Hong Kong
contact email	zfzheng@connect.hku.hk
dataset submitter

iProX dataset URI