PXD012552

PXD012552 is an original dataset announced via ProteomeXchange.

Title	XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence
Description	XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here we report POLR2A as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11-12 of XAB2 were critical for POLR2A expression. Finally we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:52:26.607.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuai Hou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-29 03:14:03	ID requested
1	2019-11-12 17:58:11	announced
⏵ 2	2024-10-22 04:52:33	announced	2024-10-22: Updated project metadata.

10.1093/nar/gkz532;

Hou S, Qu D, Li Y, Zhu B, Liang D, Wei X, Tang W, Zhang Q, Hao J, Guo W, Wang W, Zhao S, Wang Q, Azam S, Khan M, Zhao H, Zhang L, Lei H, XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence. Nucleic Acids Res, 47(15):8239-8254(2019) [pubmed]

curator keyword: Biological

submitter keyword: XAB2,POLR2A,HeLa cell

Haixin Lei
contact affiliation	Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China
contact email	haixinlei@dmu.edu.cn
lab head
Shuai Hou
contact affiliation	Dalian Medical University
contact email	houshuai009@126.com
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/2019/11/PXD012552

PRIDE project URI

• PRIDE
  1. PXD012552
     1. Label: PRIDE project
     2. Name: XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence