title: ALKBH1-Mediated tRNA Demethylation Regulates Translation.
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.
authors.affiliation: 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.
authors.forename: Fange
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Clark
authors.affiliation: 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.
authors.forename: Guanzheng
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Ye
authors.initials: Y
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Hao
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Honghui
authors.initials: H
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Dali
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Evans
authors.affiliation: 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.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Pan
authors.affiliation: 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.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000071498:AlkB Homolog 1, Histone H2a Dioxygenase / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000172:deficiency; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D012343:RNA, Transfer / Q000378:metabolism*
chemical_list: C002230:1-methyladenosine; D012343:RNA, Transfer; C499236:ALKBH1 protein, human; D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; D005947:Glucose; D000241:Adenosine
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