PXD033694

PXD033694 is an original dataset announced via ProteomeXchange.

Title	Characterization of the SF3B1 interactome
Description	CDK9 is a critical kinase required for the productive transcription of protein-coding genes by RNA polymerase II (pol II). As part of P-TEFb, CDK9 phosphorylates the carboxyl-terminal domain (CTD) of pol II and elongation factors, including SPT5, which allows pol II to elongate past the early elongation checkpoint (EEC) encountered soon after initiation. We show that, in addition to halting pol II at the EEC, loss of CDK9 activity causes premature termination of transcription across the last exon, loss of polyadenylation factors from chromatin, and loss of polyadenylation of nascent transcripts. Inhibition of the phosphatase PP2A abrogates the premature termination and loss of polyadenylation caused by CDK9 inhibition, indicating that this kinase/phosphatase pair regulates transcription elongation and RNA processing at the end of protein-coding genes. Our phosphoproteomic analyses after CDK9 inhibition, using either DRB or an analog-sensitive CDK9 cell line, confirm the splicing factor SF3B1 as an additional key target of this kinase. These results emphasize the important roles that CDK9 plays in coupling transcription elongation and termination to RNA maturation downstream of the EEC. As part of this project, we characterized the interactome of SF3B1 in HeLa cells in duplicate.
HostingRepository	PRIDE
AnnounceDate	2022-08-22
AnnouncementXML	Submission_2022-08-22_06:32:36.409.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marjorie Fournier
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-05 01:03:52	ID requested
⏵ 1	2022-08-22 06:32:37	announced

Tellier M, Zaborowska J, Neve J, Nojima T, Hester S, Fournier M, Furger A, Murphy S, CDK9 and PP2A regulate RNA polymerase II transcription termination and coupled RNA maturation. EMBO Rep, 23(10):e54520(2022) [pubmed]

submitter keyword: SF3B1, splicing, transcription, interactome

Shona Murphy
contact affiliation	Sir William Dunn School of Pathology, University of Oxford
contact email	shona.murphy@path.ox.ac.uk
lab head
Marjorie Fournier
contact affiliation	University of Oxford
contact email	marjorie.fournier@bioch.ox.ac.uk
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/2022/08/PXD033694

PRIDE project URI

• PRIDE
  1. PXD033694
     1. Label: PRIDE project
     2. Name: Characterization of the SF3B1 interactome