RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage
- Matthias Schaefer1,
- Tim Pollex1,
- Katharina Hanna1,
- Francesca Tuorto1,2,
- Madeleine Meusburger1,3,
- Mark Helm3,4 and
- Frank Lyko1,5
- 1Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg 69120, Germany;
- 2Institute of Genetics and Biophysics ABT, CNR, Naples 80131, Italy;
- 3Institute of Pharmacy and Molecular Biotechnology, Department of Chemistry, University of Heidelberg, Heidelberg 69210, Germany;
- 4Institute of Pharmacy, Johannes Gutenberg-University of Mainz, Mainz 55128, Germany
Abstract
Dnmt2 proteins are the most conserved members of the DNA methyltransferase enzyme family, but their substrate specificity and biological functions have been a subject of controversy. We show here that, in addition to tRNAAsp-GTC, tRNAVal-AAC and tRNAGly-GCC are also methylated by Dnmt2. Drosophila Dnmt2 mutants showed reduced viability under stress conditions, and Dnmt2 relocalized to stress granules following heat shock. Strikingly, stress-induced cleavage of tRNAs was Dnmt2-dependent, and Dnmt2-mediated methylation protected tRNAs against ribonuclease cleavage. These results uncover a novel biological function of Dnmt2-mediated tRNA methylation, and suggest a role for Dnmt2 enzymes during the biogenesis of tRNA-derived small RNAs.
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Footnotes
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↵5 Corresponding author.
E-MAIL f.lyko{at}dkfz.de; FAX 49-6221-423802.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.586710.
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Supplemental material is available at http://www.genesdev.org.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press