Posttranscriptional m6A Editing of HIV-1 mRNAs Enhances Viral Gene Expression

被引：291

作者：

Kennedy, Edward M. ^{[1
]}

Bogerd, Hal P. ^{[1
]}

Kornepati, Anand V. R. ^{[1
]}

Kang, Dong ^{[1
]}

Ghoshal, Delta ^{[1
]}

Marshall, Joy B. ^{[1
]}

Poling, Brigid C. ^{[1
]}

Tsai, Kevin ^{[1
]}

Gokhale, Nandan S. ^{[1
]}

Horner, Stacy M. ^{[1
,2
]}

Cullen, Bryan R. ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

来源：

CELL HOST & MICROBE | 2016年 / 19卷 / 05期

基金：

美国国家卫生研究院;

关键词：

ROUS-SARCOMA VIRUS; ADENOSYLHOMOCYSTEINE HYDROLASE; CELL TROPISM; NUCLEAR-RNA; METHYLATION; N-6-METHYLADENOSINE; N6-METHYLADENOSINE; PSEUDOURIDYLATION; 3-DEAZAADENOSINE; IDENTIFICATION;

D O I：

10.1016/j.chom.2016.04.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 30 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 identifym 6 A editing and the resultant recruitment of YTHDF proteins as major positive regulators of HIV-1 mRNA expression.

引用

页码：675 / 685

页数：11

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