PXD025763

PXD025763 is an original dataset announced via ProteomeXchange.

Title	Arginine Methylation Regulates SARS-CoV-2 Nucleocapsid Protein Function and Viral Replication
Description	Viral proteins are known to be methylated by host protein arginine methyltransferases (PRMTs) playing critical roles during viral infections. Herein, we show that PRMT1 methylates SARS-CoV-2 nucleocapsid (N) protein at residues R95 and R177 within RGG/RG sequences. Arginine methylation of N protein was confirmed by immunoblotting viral proteins extracted from SARS-CoV-2 virions isolated by cell culture. We demonstrate that arginine methylation of N protein is required for its RNA binding capacity, since treatment with a type I PRMT inhibitor (MS023) or substitution of R95K or R177K inhibited interaction with the 5’-UTR of the SARS-CoV-2 genomic RNA. We defined the N interactome in HEK293 cells with or without MS023 treatment and identified PRMT1 and many of its RGG/RG substrates including the known interactor, G3BP1, and other components of stress granules (SG). Methylation of N protein at R95 regulates another function namely its property to suppress the formation of SGs. MS023 treatment or R95K substitution blocked N-mediated suppression of SGs. Also, the co-expression of methylarginine reader TDRD3 quenched N-mediated suppression of SGs in a dose-dependent manner. Finally, pre-treatment of VeroE6 cells with MS023 significantly reduced SARS-CoV-2 replication. With type I PRMT inhibitors being in clinical trials for cancer treatment, inhibiting arginine methylation to target the later stages of the viral life cycle such as viral genome packaging and assembly of virions may be an additional therapeutic application of these drugs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:32:38.762.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025763
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stephane Richard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; phosphorylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-03 22:45:14	ID requested
1	2022-02-17 03:01:37	announced
⏵ 2	2024-10-22 05:32:46	announced	2024-10-22: Updated project metadata.

10.6019/PXD025763;

Cai T, Yu Z, Wang Z, Liang C, Richard S, Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication. J Biol Chem, 297(1):100821(2021) [pubmed]

10.1016/j.jbc.2021.100821;

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: PRMT1,SARS-CoV-2, RNA binding, stress granules, nucleocapsid (N) protein, arginine methylation, type I PRMT inhibitor, condensate, RGG/RG motif

Stephane Richard
contact affiliation	McGill University
contact email	stephane.richard@mcgill.ca
lab head
Stephane Richard
contact affiliation	McGill University
contact email	stephane.richard@mcgill.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025763
     1. Label: PRIDE project
     2. Name: Arginine Methylation Regulates SARS-CoV-2 Nucleocapsid Protein Function and Viral Replication