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@ARTICLE{Tuorto:127657,
author = {F. Tuorto$^*$ and F. Herbst$^*$ and N. Alerasool$^*$ and S.
Bender$^*$ and O. Popp and G. Federico$^*$ and S.
Reitter$^*$ and R. Liebers$^*$ and G. Stoecklin$^*$ and
H.-J. Gröne$^*$ and G. Dittmar and H. Glimm$^*$ and F.
Lyko$^*$},
title = {{T}he t{RNA} methyltransferase {D}nmt2 is required for
accurate polypeptide synthesis during haematopoiesis.},
journal = {The EMBO journal},
volume = {34},
number = {18},
issn = {1460-2075},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2017-03680},
pages = {2350 - 2362},
year = {2015},
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 = {RNA, Transfer (NLM Chemicals) / Dnmt2 protein, mouse (NLM
Chemicals) / DNA (Cytosine-5-)-Methyltransferase (NLM
Chemicals)},
cin = {A130 / G100 / A200 / G130},
ddc = {570},
cid = {I:(DE-He78)A130-20160331 / I:(DE-He78)G100-20160331 /
I:(DE-He78)A200-20160331 / I:(DE-He78)G130-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26271101},
pmc = {pmc:PMC4570521},
doi = {10.15252/embj.201591382},
url = {https://inrepo02.dkfz.de/record/127657},
}