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Genes Dev. 2010 Aug 1;24(15):1590-5. doi: 10.1101/gad.586710.

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

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  • 1Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg 69120, Germany.


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 tRNA(Asp-GTC), tRNA(Val-AAC) and tRNA(Gly-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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