Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression

被引：156

作者：

Courtney, David G. ^{[1
]}

Tsai, Kevin ^{[1
]}

Bogerd, Hal P. ^{[1
]}

Kennedy, Edward M. ^{[1
,5
]}

Law, Brittany A. ^{[2
]}

Emery, Ann ^{[3
]}

Swanstrom, Ronald ^{[3
,4
]}

Holley, Christopher L. ^{[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

[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA

[4] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27514 USA

[5] Oncorus, 50 Hampshire St,Suite 401, Cambridge, MA 02139 USA

来源：

CELL HOST & MICROBE | 2019年 / 26卷 / 02期

关键词：

MESSENGER-RNA MODIFICATIONS; N-6-METHYLADENOSINE; METHYLTRANSFERASES; 5-METHYLCYTOSINE; TRANSLATION; METHYLATION; VECTORS; BINDING;

D O I：

10.1016/j.chom.2019.07.005

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

How the covalent modification of mRNA ribonucleotides, termed epitranscriptomic modifications, alters mRNA function remains unclear. One issue has been the difficulty of quantifying these modifications. Using purified HIV-1 genomic RNA, we show that this RNA bears more epitranscriptomic modifications than the average cellular mRNA, with 5-methylcytosine (m(5)C) and 2'O-methyl modifications being particularly prevalent. The methyltransferase NSUN2 serves as the primary writer for m(5)C on HIV-1 RNAs. NSUN2 inactivation inhibits not only m(5)C addition to HIV-1 transcripts but also viral replication. This inhibition results from reduced HIV-1 protein, but not mRNA, expression, which in turn correlates with reduced ribosome binding to viral mRNAs. In addition, loss of m(5)C dysregulates the alternative splicing of viral RNAs. These data identify m(5)C as a post-transcriptional regulator of both splicing and function of HIV-1 mRNA, thereby affecting directly viral gene expression.

引用

页码：217 / +

页数：17

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