Alphaherpesvirus US3 protein-mediated inhibition of the m6A mRNA methyltransferase complex.

ABSTRACT: Chemical modifications of mRNA, the so-called epitranscriptome, represent an additional layer of post-transcriptional regulation of gene expression. The most common epitranscriptomic modification, N6-methyladenosine (m6A), is generated by a multi-subunit methyltransferase complex. We show that alphaherpesvirus kinases trigger phosphorylation of several components of the m6A methyltransferase complex, including METTL3, METTL14, and WTAP, which correlates with inhibition of the complex and a near complete loss of m6A levels in mRNA of virus-infected cells. Expression of the viral US3 protein is necessary and sufficient for phosphorylation and inhibition of the m6A methyltransferase complex. Although m6A methyltransferase complex inactivation is not essential for virus replication in cell cul

SUBMITTER: Jansens RJJ 

PROVIDER: S-EPMC9347262 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature