RNA exosome complex-mediated control of redox status in pluripotent stem cells Journal Article

Authors: Skamagki, M.; Zhang, C.; Ross, C. A.; Ananthanarayanan, A.; Liu, Z.; Mu, Q.; Basu, U.; Wang, J.; Zhao, R.; Li, H.; Kim, K.
Article Title: RNA exosome complex-mediated control of redox status in pluripotent stem cells
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. © 2017 The Authors
Keywords: reactive oxygen species; dna damage response; aging; pluripotent stem cells; glutathione; induced pluripotent stem cells; ros; gpx2; homeostatic balance; rna exosome complex
Journal Title: Stem Cell Reports
Volume: 9
Issue: 4
ISSN: 2213-6711
Publisher: Cell Press  
Date Published: 2017-10-10
Start Page: 1053
End Page: 1061
Language: English
DOI: 10.1016/j.stemcr.2017.08.024
PROVIDER: scopus
PMCID: PMC5639470
PUBMED: 29020613
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Kitai Kim
    13 Kim