PXD046082-1

PXD046082 is an original dataset announced via ProteomeXchange.

Title	A PRMT5-ZNF326 axis mediates innate immune activation upon replication stress
Description	DNA replication stress (RS) is a widespread phenomenon in carcinogenesis, causing genomic instability and extensive chromatin alterations. DNA damage leads to activation of innate immune signaling, but little is known about transcriptional regulators mediating such signaling upon RS. Using a chemical screen, we identified protein arginine methyltransferase 5 (PRMT5) as a key mediator of RS-dependent induction of interferon-stimulated genes (ISGs). This response is also associated with reactivation of endogenous retroviruses (ERVs). Using quantitative mass spectrometry, we identify proteins with PRMT5-dependent symmetric dimethylarginine (SDMA) modification induced upon RS. Among these, we show that PRMT5 targets and modulates the activity of ZNF326, a zinc finger protein essential for ISG response. Our data demonstrate a role for PRMT5-mediated SDMA in the context of RS-induced transcriptional induction, affecting physiological homeostasis and cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2024-10-08
AnnouncementXML	Submission_2024-10-08_01:17:03.914.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dennis Kappei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	dimethylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-12 02:43:16	ID requested
⏵ 1	2024-10-08 01:17:04	announced
2	2024-10-22 07:00:53	announced	2024-10-22: Updated project metadata.

10.1126/SCIADV.ADM9589;

submitter keyword: PRMT5, immune activation, SDMA, replication stress

Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore (CSI), National University of Singapore (NUS)
contact email	dennis.kappei@nus.edu.sg
lab head
Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore
contact email	dennis.kappei@nus.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046082
     1. Label: PRIDE project
     2. Name: A PRMT5-ZNF326 axis mediates innate immune activation upon replication stress