Alphaherpesvirus US3 protein-mediated inhibition of the m6A mRNA methyltransferase complex. Academic Article uri icon

Overview

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 culture, the consensus m6A methylation motif is under-represented in alphaherpesvirus genomes, suggesting evolutionary pressure against methylation of viral transcripts. Together, these findings reveal that phosphorylation can be associated with inactivation of the m6A methyltransferase complex, in this case mediated by the viral US3 protein.

publication date

  • July 19, 2022

Research

keywords

  • Adenosine
  • Methyltransferases

Identity

PubMed Central ID

  • PMC9347262

Scopus Document Identifier

  • 85134741840

Digital Object Identifier (DOI)

  • 10.1002/iid3.396

PubMed ID

  • 35858564

Additional Document Info

volume

  • 40

issue

  • 3