AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells

Yuko Ueda; Ikumi Ooshio; Yasuyuki Fusamae; Kaori Kitae; Megumi Kawaguchi; Kentaro Jingushi; Hiroaki Hase; Kazuo Harada; Kazumasa HIRATA; Kazutake Tsujikawa

doi:10.1038/srep42271

journal article Open Access Feb 13, 2017

AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells

Yuko Ueda Ikumi Ooshio Yasuyuki Fusamae Kaori Kitae Megumi Kawaguchi Kentaro Jingushi Hiroaki Hase Kazuo Harada

Kazumasa HIRATA Kazutake Tsujikawa

Scientific Reports Vol. 7 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep42271

Abstract

AbstractThe mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression. In this study, we found that ALKBH3 effectively demethylated 1-meA and 3-meC within endogenously methylated RNA. Moreover, using highly purified recombinant ALKBH3, we identified N6-methyladenine (N6-meA) in mammalian transfer RNA (tRNA) as a novel ALKBH3 substrate. An in vitro translation assay showed that ALKBH3-demethylated tRNA significantly enhanced protein translation efficiency. In addition, ALKBH3 knockdown in human cancer cells impaired cellular proliferation and suppressed the nascent protein synthesis that is usually accompanied by accumulation of the methylated RNAs. Thus, our data highlight a novel role for ALKBH3 in tumor progression via RNA demethylation and subsequent protein synthesis promotion.

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Details

Published: Feb 13, 2017
Vol/Issue: 7(1)
License: View

Authors

Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamadaoka, Suita 565-0871, Osaka, Japan

K

Kazumasa HIRATA

Graduate School of Pharmaceutical Sciences, Osaka University

K

Kazutake Tsujikawa

Cite This Article

Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, et al. (2017). AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. Scientific Reports, 7(1). https://doi.org/10.1038/srep42271

AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells

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