RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage

  1. Frank Lyko1,5
  1. 1Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg 69120, Germany;
  2. 2Institute of Genetics and Biophysics ABT, CNR, Naples 80131, Italy;
  3. 3Institute of Pharmacy and Molecular Biotechnology, Department of Chemistry, University of Heidelberg, Heidelberg 69210, Germany;
  4. 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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