转移RNA
甲基化
生物
DNA甲基化
核糖核酸
胞嘧啶
蛋白质生物合成
遗传学
分子生物学
甲基转移酶
生物化学
DNA
基因
基因表达
作者
Francesca Tuorto,Reinhard Liebers,Tanja Musch,Matthias Schaefer,Sarah Hofmann,Stefanie Kellner,Michaela Frye,Mark Helm,Georg Stoecklin,Frank Lyko
摘要
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.
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