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PMID: 27572442 Published · epublish English Journal Article

Dynamics of the human and viral m(6)A RNA methylomes during HIV-1 infection of T cells.

Nature microbiology ·Vol. 1 ·2016-02-22 ·Pages 16011

Lichinchi G, Gao S, Saletore Y, Gonzalez GM, Bansal V, Wang Y, Mason CE, Rana TM

Abstract

N(6)-methyladenosine (m(6)A) is the most prevalent internal modification of eukaryotic mRNA. Very little is known of the function of m(6)A in the immune system or its role in host-pathogen interactions. Here, we investigate the topology, dynamics and bidirectional influences of the viral-host RNA methylomes during HIV-1 infection of human CD4 T cells. We show that viral infection triggers a massive increase in m(6)A in both host and viral mRNAs. In HIV-1 mRNA, we identified 14 methylation peaks in coding and noncoding regions, splicing junctions and splicing regulatory sequences. We also identified a set of 56 human gene transcripts that were uniquely methylated in HIV-1-infected T cells and were enriched for functions in viral gene expression. The functional relevance of m(6)A for viral replication was demonstrated by silencing of the m(6)A writer or the eraser enzymes, which decreased or increased HIV-1 replication, respectively. Furthermore, methylation of two conserved adenosines in the stem loop II region of HIV-1 Rev response element (RRE) RNA enhanced binding of HIV-1 Rev protein to the RRE in vivo and influenced nuclear export of RNA. Our results identify a new mechanism for the control of HIV-1 replication and its interaction with the host immune system.

MeSH Terms
Adenosine/analogs & derivatives,analysis CD4-Positive T-Lymphocytes/chemistry,virology Cell Line HIV-1/growth & development Host-Pathogen Interactions Humans RNA, Messenger/analysis
Chemicals
RNA, Messenger N-methyladenosine Adenosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lichinchi Gianluigi
Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California 92093, USA. | Program for RNA Biology and Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Gao Shang
Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California 92093, USA.
Saletore Yogesh
Department of Physiology and Biophysics and the Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, 1305 York Avenue, New York, New York 10021, USA.
Gonzalez Gwendolyn Michelle ORCID
Environmental Toxicology Graduate Program and Department of Chemistry, University of California, Riverside, California 92521, USA.
Bansal Vikas
Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California 92093, USA.
Wang Yinsheng
Environmental Toxicology Graduate Program and Department of Chemistry, University of California, Riverside, California 92521, USA.
Mason Christopher E
Department of Physiology and Biophysics and the Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, 1305 York Avenue, New York, New York 10021, USA. | The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, The Feil Family Brain and Mind Research Institute (BMRI), New York, New York, 10021, USA.
Rana Tariq M
Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California 92093, USA. | Program for RNA Biology and Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. | Institute for Genomic Medicine and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.
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Article Info
Journal
Nature microbiology
Abbr.
Nat Microbiol
ISSN
2058-5276
DOI
10.1038/nmicrobiol.2016.11
Published
2016-02-22
Epub
2016-00-22
Pages
16011
Language
English
Region
England
NLM ID
101674869
PMCID
PMC6053355
Subset
IM
Grants
NIDA NIH HHS · DP1 DA039562 · United States
NIAID NIH HHS · R01 AI043198 · United States
NIAID NIH HHS · R21 AI125103 · United States
Corrections
CommentIn
PMID: 27572449
External Links
PubMed source DOI: 10.1038/nmicrobiol.2016.11 PMC Full Text View journal details
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