Epitranscriptomic Addition of m⁵C to HIV-1 Transcripts Regulates Viral Gene Expression.

ABSTRACT: How the covalent modification of mRNA ribonucleotides, termed epitranscriptomic modifications, alters mRNA function remains unclear. One issue has been the difficulty of quantifying these modifications. Using purified HIV-1 genomic RNA, we show that this RNA bears more epitranscriptomic modifications than the average cellular mRNA, with 5-methylcytosine (m⁵C) and 2'O-methyl modifications being particularly prevalent. The methyltransferase NSUN2 serves as the primary writer for m⁵C on HIV-1 RNAs. NSUN2 inactivation inhibits not only m⁵C addition to HIV-1 transcripts but also viral replication. This inhibition results from reduced HIV-1 protein, but not mRNA, expression, which in turn correlates with reduced ribosome binding to viral mRNAs. In addition, loss

SUBMITTER: Courtney DG 

PROVIDER: S-EPMC6714563 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature