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Nat Struct Mol Biol. 2012 Sep;19(9):900-5. doi: 10.1038/nsmb.2357. Epub 2012 Aug 12.

RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.

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  • 1Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

Abstract

The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylated tRNAs were substantially reduced, and loss of Dnmt2 and NSun2 was further associated with reduced rates of overall protein synthesis. These results establish a biologically important function for cytosine-C5 tRNA methylation in mammals and suggest that this modification promotes mouse development by supporting protein synthesis.

PMID:
22885326
[PubMed - indexed for MEDLINE]
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