PXD025763 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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; |
Keyword List
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 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025763
- Label: PRIDE project
- Name: Arginine Methylation Regulates SARS-CoV-2 Nucleocapsid Protein Function and Viral Replication