An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells.
An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells.
复制标题
DOI：
10.1016/j.stem.2015.04.002
复制
发表时间：
2015-06-04
期刊：
影响因子：
23.9
通讯作者：
Huang, Jing
中科院分区：
文献类型：
--
作者：
Li, Mangmang;Gou, Hongfeng;Tripathi, Brajendra K.;Huang, Jing;Jiang, Shunlin;Dubois, Wendy;Waybright, Tim;Lei, Ming;Shi, Jianxin;Zhou, Ming;Huang, Jing
保持基因组完整性对胚胎干细胞（ESC）至关重要，因为突变很容易繁殖到子细胞。胚胎干细胞对DNA损伤诱导的细胞凋亡（DIA）表现出超敏反应，以防止这种传播，尽管这种细胞凋亡反应的分子机制尚不清楚。在这里，我们报告的调节RNA Apela积极调节p53介导的DIA。Apela在小鼠胚胎干细胞中高度表达，并被p53激活抑制，Apela缺失会损害p53依赖性DIA。虽然Apela含有编码区，但这种编码能力与Apela在p53介导的DIA中的作用无关。相反，Apela作为调控RNA发挥作用，并与hnRNPL相互作用，从而阻止p53的线粒体定位和激活。总之，这些结果描述了一个由p53，Apela和hnRNPL组成的三元件负反馈回路，该回路调节p53介导的DIA，并进一步证明了调节RNA在DNA损伤后为ESC的凋亡反应增加了一层复杂性。
Maintaining genomic integrity is of paramount importance to embryonic stem cells (ESCs), as mutations are readily propagated to daughter cells. ESCs display hypersensitivity to DNA damage-induced apoptosis (DIA) to prevent such propagation, although the molecular mechanisms underlying this apoptotic response are unclear. Here, we report the regulatory RNA Apela positively regulates p53-mediated DIA. Apela is highly expressed in mouse ESCs and is repressed by p53 activation, and Apela depletion compromises p53-dependent DIA. Although Apela contains a coding region, this coding ability is dispensable for Apela’s role in p53-mediated DIA. Instead, Apela functions as a regulatory RNA and interacts with hnRNPL, which prevents the mitochondrial localization and activation of p53. Together, these results describe a tri-element negative feedback loop composed of p53, Apela, and hnRNPL that regulates p53-mediated DIA, and further demonstrate that regulatory RNAs add a layer of complexity to the apoptotic response of ESCs following DNA damage.
登录
查看更多内容
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
16
作者：
Dumitru, Raluca;Gama, Vivian;Fagan, B. Matthew;Bower, Jacquelyn J.;Swahari, Vijay;Pevny, Larysa H.;Deshmukh, Mohanish
通讯作者：
Deshmukh, Mohanish
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
11.8
作者：
Chng, Serene C.;Ho, Lena;Reversade, Bruno
通讯作者：
Reversade, Bruno
影响因子：
64.8
作者：
通讯作者：
--