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

被引：475

作者：

Tuorto, Francesca ^{[1
]}

Liebers, Reinhard ^{[1
]}

Musch, Tanja ^{[1
]}

Schaefer, Matthias ^{[1
]}

Hofmann, Sarah ^{[2
]}

Kellner, Stefanie ^{[3
]}

Frye, Michaela ^{[4
]}

Helm, Mark ^{[3
]}

Stoecklin, Georg ^{[2
]}

Lyko, Frank ^{[1
]}

机构：

[1] Deutsch Krebsforschungszentrum, Div Epigenet, D-6900 Heidelberg, Germany

[2] Deutsch Krebsforschungszentrum, Helmholtz Jr Res Grp Posttranscript Control Gene, D-6900 Heidelberg, Germany

[3] Johannes Gutenberg Univ Mainz, Inst Pharm, D-6500 Mainz, Germany

[4] Univ Cambridge, Wellcome Trust Ctr Stem Cell Res, Cambridge, England

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 09期

关键词：

DNA METHYLTRANSFERASE HOMOLOG; SACCHAROMYCES-CEREVISIAE; FISSION YEAST; TRANSLATION; STRESS; GENE; 5-METHYLCYTOSINE; IDENTIFICATION; TRNA(ASP); DECAY;

D O I：

10.1038/nsmb.2357

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：900 / 905

页数：6

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