1. Microbiology and Infectious Disease
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N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression

  1. Nagaraja Tirumuru
  2. Boxuan Simen Zhao
  3. Wuxun Lu
  4. Zhike Lu
  5. Chuan He  Is a corresponding author
  6. Li Wu  Is a corresponding author
  1. The Ohio State University, United States
  2. The University of Chicago, United States
Research Article
  • Cited 85
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Cite this article as: eLife 2016;5:e15528 doi: 10.7554/eLife.15528

Abstract

The internal N6-methyladenosine (m6A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m6A-modified cellular RNAs and affect RNA metabolism and processing. Here we show that YTHDF1-3 proteins recognize m6A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4+ T-cells. We further mapped the YTHDF1-3 binding sites in HIV-1 RNA from infected cells. We found that overexpression of YTHDF proteins in cells inhibited HIV-1 infection mainly by decreasing HIV-1 reverse transcription, while knockdown of YTHDF1-3 in cells had the opposite effects. Moreover, silencing the m6A writers decreased HIV-1 Gag protein expression in virus-producer cells, while silencing the m6A erasers increased Gag expression. Our findings suggest an important role of m6A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis.

Article and author information

Author details

  1. Nagaraja Tirumuru

    Center for Retrovirus Research, The Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Boxuan Simen Zhao

    Department of Chemistry, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wuxun Lu

    Center for Retrovirus Research, The Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhike Lu

    Department of Chemistry, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Chuan He

    Department of Chemistry, The University of Chicago, Chicago, United States
    For correspondence
    chuanhe@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Li Wu

    Center for Retrovirus Research, The Ohio State University, Columbus, United States
    For correspondence
    wu.840@osu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5468-2487

Reviewing Editor

  1. Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: February 25, 2016
  2. Accepted: June 30, 2016
  3. Accepted Manuscript published: July 2, 2016 (version 1)
  4. Version of Record published: July 26, 2016 (version 2)
  5. Version of Record updated: August 22, 2016 (version 3)
  6. Version of Record updated: September 13, 2017 (version 4)

Copyright

© 2016, Tirumuru et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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