PXD061743

PXD061743 is an original dataset announced via ProteomeXchange.

Title	Oligomerization of PRMT1 Regulated RNA-Binding Protein Cascade Promotes Pancreatic Ductal Adenocarcinoma
Description	PRMT1 is the predominant type I protein arginine methyltransferase responsible for generating monomethylarginine and asymmetric dimethylarginine (MMA and ADMA) in various protein substrates. It regulates numerous biological processes, including RNA metabolism, mRNA splicing, DNA damage repair, and chromatin dynamics. The crystal structure of rat PRMT1 has been previously reported as a homodimer; however, higher-order oligomeric species of human PRMT1 have been observed in vivo, and their structural basis remains elusive. In this study, we present the cryo-EM structure of human PRMT1 in its oligomeric form, revealing novel interfaces crucial for PRMT1 self-assembly and normal function. PRMT1 shows a strong preference for intrinsically disordered RGG/RG motifs, which are commonly found in RNA-binding proteins (RBPs), highlighting its critical role in regulating RNA metabolism. In vitro studies indicate that disrupting PRMT1 oligomerization impairs its binding affinity for RGG motif substrates, thereby reducing arginine methylation levels on these substrates. This finding emphasizes the essential role of the oligomeric state of PRMT1 in its function with RGG motif-containing RBPs. In vivo, the loss of PRMT1 oligomerization leads to decreased global ADMA levels in pancreatic ductal adenocarcinoma (PDAC) cells and inhibits PDAC tumor growth. Collectively, we propose that PRMT1 oligomerization, rather than mere dimerization, is sufficient for PRMT1-driven PDAC tumor growth,offering novel insights into the potential therapeutic targeting of PRMT1 oligomeric forms in PDAC.
HostingRepository	iProX
AnnounceDate	2025-03-12
AnnouncementXML	Submission_2025-03-12_01:01:09.713.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yaohui He
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-12 01:00:58	ID requested
⏵ 1	2025-03-12 01:01:10	announced

Dataset with its publication pending

submitter keyword: PRMT1, Oligomerization, Protein arginine methylation, RGG/RG motif, RNA-binding proteins, Pancreatic ductal adenocarcinoma

Yaohui He
contact affiliation	University of South China
contact email	2024001050@usc.edu.cn
lab head
Yaohui He
contact affiliation	University of South China
contact email	969220692@qq.com
dataset submitter

iProX dataset URI