RNA Exosome Complex-Mediated Control of Redox Status in Pluripotent Stem Cells

Maria Skamagki, Cheng Zhang, Christian A. Ross, Aparna Ananthanarayanan, Zhong Liu, Quanhua Mu, Uttiya Basu, Jiguang Wang, Rui Zhao, Hu Li, Kitai Kim

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The RNA exosome complex targets AU-rich element (ARE)-containing mRNAs in eukaryotic cells. We identified a transcription factor, ZSCAN10, which binds to the promoters of multiple RNA exosome complex subunits in pluripotent stem cells to maintain subunit gene expression. We discovered that induced pluripotent stem cell clones generated from aged tissue donors (A-iPSC) show poor expression of ZSCAN10, leading to poor RNA exosome complex expression, and a subsequent elevation in ARE-containing RNAs, including glutathione peroxidase 2 (Gpx2). Excess GPX2 leads to excess glutathione-mediated reactive oxygen species scavenging activity that blunts the DNA damage response and apoptosis. Expression of ZSCAN10 in A-iPSC recovers RNA exosome gene expression, the DNA damage response, and apoptosis. These findings reveal the central role of ZSCAN10 and the RNA exosome complex in maintaining pluripotent stem cell redox status to support a normal DNA damage response. Skamagki et al. demonstrate that ZSCAN10 regulates GPX2 expression by controlling RNA exosome complex in pluripotent stem cells. Low ZSCAN10 results in higher GPX2, which blunts DNA damage response by unbalancing ROS and glutathione, which may affect clinical utility.

Original languageEnglish (US)
Pages (from-to)1053-1061
Number of pages9
JournalStem Cell Reports
Volume9
Issue number4
DOIs
StatePublished - Oct 10 2017

Keywords

  • DNA damage response
  • GPX2
  • RNA exosome complex
  • ROS
  • aging
  • glutathione
  • homeostatic balance
  • induced pluripotent stem cells
  • pluripotent stem cells
  • reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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