RNA Exosome Complex-Mediated Control of Redox Status in Pluripotent Stem Cells.
RNA Exosome Complex-Mediated Control of Redox Status in Pluripotent Stem Cells.
复制标题
RNA外体复合体介导的多能干细胞氧化还原状态的控制。
DOI：
10.1016/j.stemcr.2017.08.024
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发表时间：
2017-10-10
影响因子：
5.9
通讯作者：
Kim K
中科院分区：
文献类型：
--
作者：
Skamagki M;Zhang C;Ross CA;Ananthanarayanan A;Liu Z;Mu Q;Basu U;Wang J;Zhao R;Li H;Kim K
RNA外泌体复合物靶向真核细胞中富含au元素（ARE）的mrna。我们发现了一个转录因子ZSCAN10，它与多能干细胞中多个RNA外显体复合物亚基的启动子结合，以维持亚基基因的表达。我们发现，由衰老组织供体（a - ipsc）产生的诱导多能干细胞克隆显示ZSCAN10的低表达，导致RNA外泌体复合物的低表达，以及随后含有are的RNA的升高，包括谷胱甘肽过氧化物酶2 （Gpx2）。过量的GPX2导致过量的谷胱甘肽介导的活性氧清除活性，从而减弱DNA损伤反应和细胞凋亡。在A-iPSC中表达ZSCAN10可恢复RNA外泌体基因表达、DNA损伤反应和细胞凋亡。这些发现揭示了ZSCAN10和RNA外泌体复合物在维持多能干细胞氧化还原状态以支持正常DNA损伤反应中的核心作用。ZSCAN10与多个RNA外显体复合物亚基的转录起始位点结合，ZSCAN10表达差的iPSCs导致RNA外显体复合物亚基表达差，因此，RNA外显体复合物核心亚基表达差会使含are的RNA升高。Skamagki等人证明，ZSCAN10通过控制多能干细胞中RNA外泌体复合体来调节GPX2的表达。低ZSCAN10导致较高的GPX2，从而减弱ROS和谷胱甘肽失衡引起的DNA损伤反应，可能影响临床应用。
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. ZSCAN10 binds to transcription start sites of multiple RNA exosome complex subunits iPSCs with poor ZSCAN10 expression cause poor expression of RNA exosome complex subunits Consequently, poor expression of RNA exosome complex core subunits elevates ARE-containing RNAs, including GPX2 Higher GPX2 blunts DNA damage response by homeostatic imbalance of ROS and glutathione 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.
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影响因子：
8.8
作者：
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