ALKBH1-Mediated tRNA Demethylation Regulates Translation

被引：376

作者：

Liu, Fange ^{[1
,2
,3
]}

Clark, Wesley ^{[2
,4
]}

Luo, Guanzheng ^{[1
,2
,3
]}

Wang, Xiaoyun ^{[2
,4
]}

Fu, Ye ^{[1
,2
,3
]}

Wei, Jiangbo ^{[1
,2
,3
]}

Wang, Xiao ^{[1
,2
,3
]}

Hao, Ziyang ^{[1
,2
,3
]}

Dai, Qing ^{[1
,2
,3
]}

Zheng, Guanqun ^{[2
,4
]}

Ma, Honghui ^{[1
,2
,3
]}

Han, Dali ^{[1
,2
,3
]}

Evans, Molly ^{[2
,4
]}

Klungland, Arne ^{[5
,6
]}

Pan, Tao ^{[2
,4
]}

He, Chuan ^{[1
,2
,3
,4
]}

机构：

[1] Univ Chicago, Dept Biochem & Mol Biol, Dept Chem, 929 East 57th St, Chicago, IL 60637 USA

[2] Univ Chicago, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA

[3] Univ Chicago, Howard Hughes Med Inst, 929 East 57th St, Chicago, IL 60637 USA

[4] Univ Chicago, Dept Biochem & Mol Biol, 929 East 57th St, Chicago, IL 60637 USA

[5] Oslo Univ Hosp, Dept Microbiol, Rikshosp, N-0027 Oslo, Norway

[6] Univ Oslo, Inst Basic Med Sci, Dept Mol Med, N-0317 Oslo, Norway

来源：

CELL | 2016年 / 167卷 / 03期

基金：

美国国家科学基金会;

关键词：

DYNAMIC N-1-METHYLADENOSINE METHYLOME; GENE-EXPRESSION REGULATION; OBESITY-ASSOCIATED FTO; MESSENGER-RNA; M(6)A RNA; POSTTRANSCRIPTIONAL MODIFICATIONS; OXIDATIVE DEMETHYLATION; ALKYLATION DAMAGE; ESCHERICHIA-COLI; STRUCTURAL BASIS;

D O I：

10.1016/j.cell.2016.09.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

tRNA is a central component of protein synthesis and the cell signaling network. One salient feature of tRNA is its heavily modified status, which can critically impact its function. Here, we show that mammalian ALKBH1 is a tRNA demethylase. It mediates the demethylation of N-1-methyladenosine (m(1)A) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis. This process is dynamic and responds to glucose availability to affect translation. Our results uncover reversible methylation of tRNA as a new mechanism of post-transcriptional gene expression regulation.

引用

页码：816 / +

页数：29

共 72 条

[1] Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA [J].