TY  - JOUR
AU  - Tuorto, Francesca
AU  - Herbst, Friederike
AU  - Alerasool, Nader
AU  - Bender, Sebastian
AU  - Popp, Oliver
AU  - Federico, Giuseppina
AU  - Reitter, Sonja
AU  - Liebers, Reinhard
AU  - Stoecklin, Georg
AU  - Gröne, Hermann-Josef
AU  - Dittmar, Gunnar
AU  - Glimm, Hanno
AU  - Lyko, Frank
TI  - The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis.
JO  - The EMBO journal
VL  - 34
IS  - 18
SN  - 1460-2075
CY  - Heidelberg
PB  - EMBO Press
M1  - DKFZ-2017-03680
SP  - 2350 - 2362
PY  - 2015
AB  - 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.
KW  - RNA, Transfer (NLM Chemicals)
KW  - Dnmt2 protein, mouse (NLM Chemicals)
KW  - DNA (Cytosine-5-)-Methyltransferase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26271101
C2  - pmc:PMC4570521
DO  - DOI:10.15252/embj.201591382
UR  - https://inrepo02.dkfz.de/record/127657
ER  -