Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression
- PMID: 27117054
- PMCID: PMC4867121
- DOI: 10.1016/j.chom.2016.04.002
Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression
Erratum in
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Posttranscriptional m6A Editing of HIV-1 mRNAs Enhances Viral Gene Expression.Cell Host Microbe. 2017 Dec 13;22(6):830. doi: 10.1016/j.chom.2017.11.010. Cell Host Microbe. 2017. PMID: 29241043 Free PMC article. No abstract available.
Abstract
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.
Copyright © 2016 Elsevier Inc. All rights reserved.
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Comment in
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Viruses, Mark Thy Message Well.Cell Host Microbe. 2016 May 11;19(5):568-70. doi: 10.1016/j.chom.2016.04.018. Cell Host Microbe. 2016. PMID: 27173921
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References
-
- Bader JP, Brown NR, Chiang PK, Cantoni GL. 3-Deazaadenosine, an inhibitor of adenosylhomocysteine hydrolase, inhibits reproduction of Rous sarcoma virus and transformation of chick embryo cells. Virology. 1978;89:494–505. - PubMed
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