PNPT1 Release from Mitochondria during Apoptosis Triggers Decay of Poly(A) RNAs
PNPT1 Release from Mitochondria during Apoptosis Triggers Decay of Poly(A) RNAs
复制标题
凋亡过程中线粒体释放的 PNPT1 触发了多聚（A）RNA 的衰变
DOI：
10.1016/j.cell.2018.04.017
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发表时间：
2018-06-28
期刊：
影响因子：
64.5
通讯作者：
Lieberman, Judy
中科院分区：
文献类型：
--
作者：
Liu, Xing;Fu, Rui;Lieberman, Judy
广泛的mRNA衰变，一种未被认识到的凋亡特征，增强了细胞死亡，并依赖于线粒体外膜透化（MOMP）、TUTases和DIS 3L 2。哪些RNA被衰变以及衰变起始事件是未知的。在这里，我们显示了在3'端的mRNA和多聚（A）非编码（nc）RNA的广泛衰减，由MOMP期间释放的线粒体膜间空间3'至5'核糖核酸外切酶PNPT 1触发。PNPT 1敲低抑制凋亡RNA衰变并减少凋亡，而PNPT 1的异位表达，但不是RNA酶缺陷突变体，增加RNA衰变和细胞死亡。PNPT 1基板的30端穿过狭窄通道。许多非poly（A）ncRNA含有3 '-二级结构或结合可能阻断PNPT 1活性的蛋白质。事实上，破坏抗衰变ncRNA的3 '-茎环的突变使转录物易感，而向mRNA添加3'-茎环可防止其衰变。因此，在MOMP期间从线粒体释放PNPT 1启动缺乏3 '-结构的RNA的凋亡衰变。
Widespread mRNA decay, an unappreciated feature of apoptosis, enhances cell death and depends on mitochondrial outer membrane permeabilization (MOMP), TUTases, and DIS3L2. Which RNAs are decayed and the decay-initiating event are unknown. Here, we show extensive decay of mRNAs and poly(A) noncoding (nc) RNAs at the 3' end, triggered by the mitochondrial intermembrane space 3'-to-5' exoribonuclease PNPT1, released during MOMP. PNPT1 knockdown inhibits apoptotic RNA decay and reduces apoptosis, while ectopic expression of PNPT1, but not an RNase-deficient mutant, increases RNA decay and cell death. The 3 0 end of PNPT1 substrates thread through a narrow channel. Many non-poly(A) ncRNAs contain 3'-secondary structures or bind proteins that may block PNPT1 activity. Indeed, mutations that disrupt the 3'-stemloop of a decay-resistant ncRNA render the transcript susceptible, while adding a 3'-stem-loop to an mRNA prevents its decay. Thus, PNPT1 release from mitochondria during MOMP initiates apoptotic decay of RNAs lacking 3'-structures.