ALKBH1-Mediated tRNA Demethylation Regulates Translation

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 N1-methyladenosine (m1A)...

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Bibliographic Details
Published in:Cell 2016-10, Vol.167 (3), p.816-828.e16
Main Authors: Liu, Fange, Clark, Wesley, Luo, Guanzheng, Wang, Xiaoyun, Fu, Ye, Wei, Jiangbo, Wang, Xiao, Hao, Ziyang, Dai, Qing, Zheng, Guanqun, Ma, Honghui, Han, Dali, Evans, Molly, Klungland, Arne, Pan, Tao, He, Chuan
Format: Article
Language:English
Subjects:
Adenosine - analogs & derivatives
Adenosine - metabolism
AlkB Homolog 1, Histone H2a Dioxygenase - genetics
AlkB Homolog 1, Histone H2a Dioxygenase - metabolism
ALKBH1
codon usage
dynamic tRNA modification
Gene Expression Regulation
glucose
Glucose - deficiency
HeLa Cells
Humans
mammals
Methylation
N1-methyladenosine (m1A)
Polyribosomes - metabolism
Protein Biosynthesis - genetics
protein synthesis
RNA, Transfer - metabolism
transfer RNA
translation elongation
translation initiation
translation regulation
tRNA demethylase
tRNA demethylation
tRNA methylation
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Summary: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 N1-methyladenosine (m1A) 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. [Display omitted] •ALKBH1 catalyzes the demethylation of m1A in tRNA•The m1A demethylation affects the tRNAiMet level and translation initiation•The ALKBH1-mediated tRNA demethylation attenuates translation elongation•Reversible tRNA methylation dynamically regulates translation Reversible tRNA methylation facilitates translation response to nutrient availability.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2016.09.038