PXD064804-1
PXD064804 is an original dataset announced via ProteomeXchange.
Dataset Summary
| 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_2025-06-09_23:42:00.139.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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-06-09 23:41:46 | ID requested | |
| ⏵ 1 | 2025-06-09 23:42:00 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Neural crest development, Splicing factors |
Contact List
| 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 | |
Full Dataset Link List
| iProX dataset URI |
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