ALKBH1-Mediated tRNA Demethylation Regulates Translation

Fange Liu; Wesley Clark; Guanzheng Luo; Xiaoyun Wang; Ye Fu; Jiangbo Wei; Xiao Wang; Ziyang Hao; Qing Dai; Guanqun Zheng; Honghui Ma; Dali Han; Molly Evans; Arne Klungland; Tao Pan; Chuan He

doi:10.1016/j.cell.2016.09.038

ALKBH1-Mediated tRNA Demethylation Regulates Translation

Cell. 2016 Oct 20;167(3):816-828.e16. doi: 10.1016/j.cell.2016.09.038. Epub 2016 Oct 13.

Authors

Fange Liu¹, Wesley Clark², Guanzheng Luo¹, Xiaoyun Wang², Ye Fu¹, Jiangbo Wei¹, Xiao Wang¹, Ziyang Hao¹, Qing Dai¹, Guanqun Zheng², Honghui Ma¹, Dali Han¹, Molly Evans², Arne Klungland³, Tao Pan⁴, Chuan He⁵

Affiliations

¹ Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
² Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
³ Department of Microbiology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
⁴ Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA. Electronic address: taopan@uchicago.edu.
⁵ Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA. Electronic address: chuanhe@uchicago.edu.

Abstract

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.

Keywords: ALKBH1; N(1)-methyladenosine (m(1)A); codon usage; dynamic tRNA modification; tRNA demethylase; tRNA demethylation; tRNA methylation; translation elongation; translation initiation; translation regulation.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenosine / analogs & derivatives
Adenosine / metabolism
AlkB Homolog 1, Histone H2a Dioxygenase / genetics
AlkB Homolog 1, Histone H2a Dioxygenase / metabolism*
Gene Expression Regulation*
Glucose / deficiency
HeLa Cells
Humans
Methylation
Polyribosomes / metabolism
Protein Biosynthesis / genetics*
RNA, Transfer / metabolism*

Substances

1-methyladenosine
RNA, Transfer
ALKBH1 protein, human
AlkB Homolog 1, Histone H2a Dioxygenase
Glucose
Adenosine

Abstract

Publication types

MeSH terms

Substances

Grants and funding