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The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis

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Item Type:Article
Title:The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis
Creators Name:Tuorto, F. and Herbst, F. and Alerasool, N. and Bender, S. and Popp, O. and Federico, G. and Reitter, S. and Liebers, R. and Stoecklin, G. and Groene, H.J. and Dittmar, G. and Glimm, H. and Lyko, F.
Abstract:The Dnmt2 enzyme utilizes the catalytic mechanism of eukaryotic DNA methyltransferases to methylate several tRNAs at cytosine 38. Dnmt2 mutant mice, flies, and plants were reported to be viable and fertile, and the biological function of Dnmt2 has remained elusive. Here, we show that endochondral ossification is delayed in newborn Dnmt2-deficient mice, which is accompanied by a reduction of the haematopoietic stem and progenitor cell population and a cell-autonomous defect in their differentiation. RNA bisulfite sequencing revealed that Dnmt2 methylates C38 of tRNA Asp(GTC), Gly(GCC), and Val(AAC), thus preventing tRNA fragmentation. Proteomic analyses from primary bone marrow cells uncovered systematic differences in protein expression that are due to specific codon mistranslation by tRNAs lacking Dnmt2-dependent methylation. Our observations demonstrate that Dnmt2 plays an important role in haematopoiesis and define a novel function of C38 tRNA methylation in the discrimination of near-cognate codons, thereby ensuring accurate polypeptide synthesis.
Keywords:(Cytosine-5) tRNA Methylation, Dnmt2, Haematopoiesis, MSCs, Translation Fidelity, Animals, Mice
Source:EMBO Journal
Publisher:EMBO Press / Wiley
Page Range:2350-2362
Date:14 September 2015
Official Publication:https://doi.org/10.15252/embj.201591382
PubMed:View item in PubMed

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