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

Published

Journal Article

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 of m5C dysregulates the alternative splicing of viral RNAs. These data identify m5C as a post-transcriptional regulator of both splicing and function of HIV-1 mRNA, thereby affecting directly viral gene expression.

Full Text

Duke Authors

Cited Authors

  • Courtney, DG; Tsai, K; Bogerd, HP; Kennedy, EM; Law, BA; Emery, A; Swanstrom, R; Holley, CL; Cullen, BR

Published Date

  • August 14, 2019

Published In

Volume / Issue

  • 26 / 2

Start / End Page

  • 217 - 227.e6

PubMed ID

  • 31415754

Pubmed Central ID

  • 31415754

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2019.07.005

Language

  • eng

Conference Location

  • United States