PXD051128-2

PXD051128 is an original dataset announced via ProteomeXchange.

Title	GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies
Description	Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing, but therapeutic means to correct this mis-splicing do not exist. Here, we utilize synthetic introns uniquely responsive to mutant SF3B1 to identify trans factors required for aberrant mutant SF3B1 splicing activity. This revealed the G-patch domain-containing protein GPATCH8 as required for mutant SF3B1-induced splicing alterations and impaired hematopoiesis. GPATCH8 is involved in quality control of branchpoint selection, interacts with the RNA helicase DHX15, and functionally opposes SUGP1, a G-patch protein recently implicated in SF3B1-mutant diseases. Silencing of GPATCH8 corrected one-third of mutant SF3B1-dependent splicing defects and was sufficient to improve dysfunctional hematopoiesis in SF3B1-mutant mouse and primary human progenitors. These data identify GPATCH8 as a novel splicing factor required for mis-splicing by mutant SF3B1 and highlight the therapeutic impact of correcting aberrant splicing in SF3B1-mutant cancers.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:35:47.614.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhuoning Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-01 09:59:33	ID requested
1	2024-04-10 07:56:55	announced
⏵ 2	2024-10-22 06:35:48	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: SF3B1, SUGP1, Splicing,DHX15, GPATCH8, Leukemia, Myelodysplastic Syndromes, RNA, G-patch domain

Omar Abdel-Wahab
contact affiliation	Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States
contact email	abdelwao@mskcc.org
lab head
Zhuoning Li
contact affiliation	MSKCC
contact email	liz2@mskcc.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/04/PXD051128

PRIDE project URI

• PRIDE
  1. PXD051128
     1. Label: PRIDE project
     2. Name: GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies