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Deficiency in a glutamine-specific methyltransferase for release factor causes mouse embryonic lethality.

Authors
  • Liu, Peng1
  • Nie, Song
  • Li, Bing
  • Yang, Zhong-Qiang
  • Xu, Zhi-Mei
  • Fei, Jian
  • Lin, Chyuansheng
  • Zeng, Rong
  • Xu, Guo-Liang
  • 1 The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China. , (China)
Type
Published Article
Journal
Molecular and Cellular Biology
Publisher
American Society for Microbiology
Publication Date
Sep 01, 2010
Volume
30
Issue
17
Pages
4245–4253
Identifiers
DOI: 10.1128/MCB.00218-10
PMID: 20606008
Source
Medline
License
Unknown

Abstract

Biological methylation is a fundamental enzymatic reaction for a variety of substrates in multiple cellular processes. Mammalian N6amt1 was thought to be a homologue of bacterial N(6)-adenine DNA methyltransferases, but its substrate specificity and physiological importance remain elusive. Here, we demonstrate that N6amt1 functions as a protein methyltransferase for the translation termination factor eRF1 in mammalian cells both in vitro and in vivo. Mass spectrometry analysis indicated that about 70% of the endogenous eRF1 is methylated at the glutamine residue of the conserved GGQ motif. To address the physiological significance of eRF1 methylation, we disrupted the N6amt1 gene in the mouse. Loss of N6amt1 led to early embryonic lethality. The postimplantation development of mutant embryos was impaired, resulting in degeneration around embryonic day 6.5. This is in contrast to what occurs in Escherichia coli and Saccharomyces cerevisiae, which can survive without the N6amt1 homologues. Thus, N6amt1 is the first glutamine-specific protein methyltransferase characterized in vivo in mammals and methylation of eRF1 by N6amt1 might be essential for the viability of early embryos.

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