RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage.
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.
Schaefer
Matthias
M
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg 69120, Germany.
Pollex
Tim
T
Hanna
Katharina
K
Tuorto
Francesca
F
Meusburger
Madeleine
M
Helm
Mark
M
Lyko
Frank
F
D000818:Animals; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D008745:Methylation; D051379:Mice; D012313:RNA / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D013312:Stress, Physiological; D016019:Survival Analysis
D029721:Drosophila Proteins; D012313:RNA; D012343:RNA, Transfer; C491784:Mt2 protein, Drosophila; D004248:DNA (Cytosine-5-)-Methyltransferases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic