Arginine methyltransferase PRMT5 negatively regulates cGAS-mediated antiviral immune response.
Sci Adv
; 7(13)2021 03.
Article
em En
| MEDLINE
| ID: mdl-33762328
ABSTRACT
Cyclic GMP-AMP synthase (cGAS) functions as an essential DNA sensor, which senses the cytoplasmic double-stranded DNA and activates the antiviral response. However, the posttranslational modification of cGAS remains to be fully understood and whether it has arginine methylation modification remains unknown. Here, we identified protein arginine methyltransferase 5 (PRMT5) as a direct binding partner of cGAS, and it catalyzed the arginine symmetrical dimethylation of cGAS at the Arg124 residue. Further investigation demonstrated that methylation of cGAS by PRMT5 attenuated cGAS-mediated antiviral immune response by blocking the DNA binding ability of cGAS. Oral administration of PRMT5 inhibitors significantly protected mice from HSV-1 infection and prolonged the survival time of these infected mice. Therefore, our findings revealed an essential regulatory effect of PRMT5 on cGAS-mediated antiviral immune response and provided a promising potential antiviral strategy by modulating PRMT5.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
/
Herpes Simples
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article