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NORAD lncRNA组装了一个对基因组稳定性至关重要的拓酶复合体
Mathias Munschauer1, Celina T Nguyen2, Klara Sirokman2
1Broad Institute of MIT and Harvard, Cambridge, MA, USA. mathias@broadinstitute.org.
Nature
|August 29, 2018
概括
长非编码RNA NORAD通过结合RBMX形成NARC1复合体来保持基因组稳定性,其中包括TOP1和PRPF19-CDC5L. 这种相互作用对DNA修复和预防染色体不稳定至关重要.
科学领域:
- 分子生物学
- 遗传学
- 核糖核酸生物学
背景情况:
- 数以千计的长非编码RNAs (lncRNAs) 存在,但很少有人知道它们的功能.
- NORAD (通过DNA损伤激活的非编码RNA) 与基因组稳定性有关,但其机制尚不清楚.
研究的目的:
- 为了确定与NORAD相互作用的蛋白质.
- 阐明NORAD在保持基因组稳定的分子机制.
主要方法:
- 与定量质谱相结合的RNA反意义净化
- 细胞耗尽和救援实验
主要成果:
- 与包括RBMX在内的DNA复制和修复蛋白相互作用.
- NORAD对于组装包含TOP1,ALYREF和PRPF19- CDC5L复合物的NARC1复合物 (NORAD激活的核蛋白复合物1) 是必不可少的.
- NORAD或RBMX的耗尽导致染色体分离缺陷和细胞周期进展的改变.
结论:
- 在基因组稳定性方面,NORAD-RBMX相互作用对NORAD的功能至关重要.
- NORAD促进了NARC1复合体的组装,这是一个对基因组完整性至关重要的新型拓酶复合体.
- lncRNAs在调节RNA结合蛋白质复合物的过程中发挥作用.
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