Early embryonic lethality of mice with disrupted transcription cofactor PIMT/NCOA6IP/Tgs1 gene

Yuzhi Jia, Navin Viswakarma, Susan E. Crawford, Joy Sarkar, M. Sambasiva Rao, William J. Karpus, Yashpal S. Kanwar, Yi Jun Zhu*, Janardan K. Reddy

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

PIMT (also known as PIPMT/NCOA6IP/Tgs1), first isolated as a transcription coactivator PRIP (NCOA6)-interacting 96-kDa protein with RNA-binding property, possesses RNA methyltransferase activity. As a transcription coactivator binding protein, PIMT enhances the nuclear receptor transcriptional activity and its methyltransferase property is involved in the formation of the 2,2,7-trimethylguanosine cap of non-coding small RNAs, but the in vivo functions of this gene have not been fully explored. To elucidate the biological functions, we used gene targeting to generate mice with a disrupted PIMT/Tgs1 gene. Disruption of PIMT gene results in early embryonic lethality due to impairment of development around the blastocyst and uterine implantation stages. We show that PIMT is expressed in all cells of the E3.5day blastocyst in the mouse. PIMT null mutation abolished PIMT expression in all cells of the blastocyst and caused a reduction in the expression of Oct4 and Nanog transcription factor proteins in the E3.5 blastocyst resulting in the near failure to form inner cell mass (ICM). With conditional deletion of PIMT gene, mouse embryonic fibroblasts (MEFs) exhibit defective wound healing in the scratch assay and a reduction in cell proliferation due to decreased G0/G1 transition and G2/M phase cell cycle arrest. We conclude that PIMT/NCOA6IP, which is expressed in all cells of the 3.5day stage blastocyst, is indispensable for early embryonic development.

Original languageEnglish (US)
Pages (from-to)193-207
Number of pages15
JournalMechanisms of Development
Volume129
Issue number9-12
DOIs
StatePublished - Sep 1 2012

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Keywords

  • Apoptosis
  • Blastocyst
  • Embryonic lethality
  • G/M phase arrest
  • PIMT/NCOA6IP/Tgs1

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

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