ALKBH1-Mediated tRNA Demethylation Regulates Translation

  • Cell. 2016 Oct 20;167(3):816-828.e16. doi: 10.1016/j.cell.2016.09.038.
Fange Liu  1 ,  Wesley Clark  2 ,  Guanzheng Luo  1 ,  Xiaoyun Wang  2 ,  Ye Fu  1 ,  Jiangbo Wei  1 ,  Xiao Wang  1 ,  Ziyang Hao  1 ,  Qing Dai  1 ,  Guanqun Zheng  2 ,  Honghui Ma  1 ,  Dali Han  1 ,  Molly Evans  2 ,  Arne Klungland  3 ,  Tao Pan  4 ,  Chuan He  5
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: [email protected].
  • 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: [email protected].
PMID: 27745969 DOI: 10.1016/j.cell.2016.09.038
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.