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- Title
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.
- Authors
Tuorto, Francesca; Liebers, Reinhard; Musch, Tanja; Schaefer, Matthias; Hofmann, Sarah; Kellner, Stefanie; Frye, Michaela; Helm, Mark; Stoecklin, Georg; Lyko, Frank
- 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.
- Publication
Nature structural & molecular biology, 2012, Vol 19, Issue 9, p900
- ISSN
1545-9985
- Publication type
Journal Article
- DOI
10.1038/nsmb.2357