Proteomics

Dataset Information

0

Arginine Methylation Regulates SARS-CoV-2 Nucleocapsid Protein Function and Viral Replication


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Stephane Richard  

LAB HEAD: Stephane Richard

PROVIDER: PXD025763 | Pride | 2022-02-17

REPOSITORIES: Pride

Dataset's files

Source:
altmetric image

Publications

Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication.

Cai Ting T   Yu Zhenbao Z   Wang Zhen Z   Liang Chen C   Richard Stéphane S  

The Journal of biological chemistry 20210523 1


Viral proteins are known to be methylated by host protein arginine methyltransferases (PRMTs) necessary for the viral life cycle, but it remains unknown whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins are methylated. Herein, we show that PRMT1 methylates SARS-CoV-2 nucleocapsid (N) protein at residues R95 and R177 within RGG/RG motifs, preferred PRMT target sequences. We confirmed arginine methylation of N protein by immunoblotting viral proteins extracted from SARS  ...[more]

Similar Datasets

2022-03-03 | PXD031057 | Pride
2023-10-26 | GSE246325 | GEO
2024-10-21 | GSE274754 | GEO
2024-10-21 | PXD055018 | JPOST Repository
2015-09-18 | E-GEOD-73177 | biostudies-arrayexpress
2021-08-01 | GSE158625 | GEO
2023-06-16 | GSE234807 | GEO
2021-11-10 | GSE122435 | GEO
2014-10-31 | E-GEOD-52920 | biostudies-arrayexpress
2023-10-02 | GSE212049 | GEO