Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression.

Published

Journal Article

Covalent addition of a methyl group to adenosine N(6) (m(6)A) is an evolutionarily conserved and common RNA modification that is thought to modulate several aspects of RNA metabolism. While the presence of multiple m(6)A editing sites on diverse viral RNAs was reported starting almost 40 years ago, how m(6)A editing affects virus replication has remained unclear. Here, we used photo-crosslinking-assisted m(6)A sequencing techniques to precisely map several m(6)A editing sites on the HIV-1 genome and report that they cluster in the HIV-1 3' untranslated region (3' UTR). Viral 3' UTR m(6)A sites or analogous cellular m(6)A sites strongly enhanced mRNA expression in cis by recruiting the cellular YTHDF m(6)A "reader" proteins. Reducing YTHDF expression inhibited, while YTHDF overexpression enhanced, HIV-1 protein and RNA expression, and virus replication in CD4+ T cells. These data identify m(6)A editing and the resultant recruitment of YTHDF proteins as major positive regulators of HIV-1 mRNA expression.

Full Text

Duke Authors

Cited Authors

  • Kennedy, EM; Bogerd, HP; Kornepati, AVR; Kang, D; Ghoshal, D; Marshall, JB; Poling, BC; Tsai, K; Gokhale, NS; Horner, SM; Cullen, BR

Published Date

  • May 2016

Published In

Volume / Issue

  • 19 / 5

Start / End Page

  • 675 - 685

PubMed ID

  • 27117054

Pubmed Central ID

  • 27117054

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

International Standard Serial Number (ISSN)

  • 1931-3128

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2016.04.002

Language

  • eng