在亡过程中从线粒体释放的PNPT1触发了多ARNA的衰变
Xing Liu1, Rui Fu1, Youdong Pan2
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|May 22, 2018
概括
在细胞亡过程中,线粒体释放PNPT1会引发广泛的RNA衰变,从而增强细胞死亡. 这一过程针对特定的RNA,揭示了细胞死亡的新机制.
科学领域:
- 细胞生物学
- 分子生物学
- 生物化学
背景情况:
- 广泛的mRNA衰变是亡的一个关键,但尚未研究的组成部分.
- 核突的RNA衰变依赖于线粒体外膜透 (MOMP),TUTases和DIS3L2.
- 特定的向RNA和开始亡的事件在很大程度上是未知的.
研究的目的:
- 识别在亡过程中发生衰变的RNA.
- 阐明启动分子事件引发广泛的RNA衰变.
- 了解线粒体因子在阿波性RNA衰变中的作用.
主要方法:
- 通过对线粒体蛋白质的破坏和过度表达,研究了亡过程中的RNA衰变.
- 使用RNase测定和结构分析来确定PNPT1基质的特异性.
- 研究了RNA3'末端结构对衰变易感性的影响.
主要成果:
- 鉴定了PNPT1,一个线粒体外核酶,作为在亡过程中广泛的mRNA和非编码RNA衰变的触发物.
- 在MOMP过程中释放PNPT1可启动缺乏保护结构的RNA的3'端衰变.
- 破坏RNA 3'干循环结构会增强衰变,而添加它们会赋予耐药性.
结论:
- 在MOMP过程中从线粒体释放PNPT1是阿波性RNA衰变的启动事件.
- 核突性RNA衰变主要针对具有可访问的3'末端的RNA,例如mRNA和多种类型的非编码RNA.
- RNA结构元素决定了对PNPT1媒介衰变的易感性,突出显示了亡中的调节机制.
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