RNA Exosome Complex-Mediated Control of Redox Status in Pluripotent Stem Cells.
Stem Cell Reports
; 9(4): 1053-1061, 2017 10 10.
Article
em En
| MEDLINE
| ID: mdl-29020613
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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Oxirredução
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Células-Tronco Pluripotentes
/
Complexo Multienzimático de Ribonucleases do Exossomo
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2017
Tipo de documento:
Article