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非编码RNA NORAD通过隔离PUMILIO蛋白来调节基因组稳定性
Sungyul Lee1, Florian Kopp2, Tsung-Cheng Chang2
1Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA; Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|January 4, 2016
概括
通过控制PUMILIO蛋白质,长非编码RNANORAD保持了基因组的稳定性. 它的缺失导致形,突显了NORAD在预防染色体不稳定的关键作用.
科学领域:
- 分子生物学
- 遗传学
- 基因组学
背景情况:
- 长非编码RNAs (lncRNAs) 调节许多生物过程.
- 包括LINC00657在内的许多lncRNA的功能尚不清楚.
- DNA 损伤可以诱导特定的 lncRNA 表达.
研究的目的:
- 为了功能性地描述 lncRNA LINC00657,称为NORAD (由DNA损伤激活的非编码RNA).
- 调查NORAD在维持基因组稳定的作用.
- 阐明NORAD如何影响PUMILIO蛋白的活性.
主要方法:
- 在人类细胞系中对LINC00657 (NORAD) 的功能分析.
- 评估动质积分和染色体不稳定性
- 研究PUMILIO蛋白的相互作用和功能.
- 通过PUMILIO蛋白调节的mRNA目标的分析.
主要成果:
- NORAD是一个高度保存和丰富的 lncRNA 诱导DNA损伤.
- 在稳定的细胞系中,NORAD的无活化会导致显著的无体积变异.
- 通过隔离PUMILIO蛋白质来保持基因组稳定性.
- 缺少NORAD会导致PUMILIO蛋白过活,通过抑制关键细胞循环和修复因子导致染色体不稳定.
结论:
- 在保持基因组稳定性方面发挥关键作用.
- NORAD调节PUMILIO蛋白的活性,这是一个保存的RNA结合蛋白家族.
- 通过NORAD监管的PUMILIO蛋白质对于预防染色体不稳定至关重要.
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