基因组稳定性需要NORAD诱导的Pumilio阶段分离
Mahmoud M Elguindy1,2, Joshua T Mendell3,4,5,6
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|June 10, 2021
概括
长非编码RNA NORAD使用相分离来抑制Pumilio蛋白质,保持基因组稳定性. 破坏这种由RNA驱动的过程会导致基因组不稳定, 这突显了它在细胞调节中的关键作用.
科学领域:
- 细胞生物学
- 分子生物学
- 遗传学
背景情况:
- 液体与液体相的分离驱动了亚细胞组织.
- RNA代谢受到分相RNA凝聚物的影响.
- 特定RNA通过相分离调节RNA结合蛋白 (RBPs) 的机制尚不清楚.
研究的目的:
- 研究调节RBP活动中的RNA驱动相分离.
- 确定长非编码RNA (lncRNA) NORAD在控制Pumilio (PUM) 蛋白中的作用.
- 阐明NORAD介导阶段分离在维持基因组稳定性的作用.
主要方法:
- 研究了NORAD与哺乳动物细胞中的PUM蛋白的相互作用.
- 研究了NORAD核化的PUM凝聚物 (NP体) 的形成.
- 评估了破坏NORAD驱动的相分离对PUM活动和基因组稳定性的影响.
- 使用合成RNA来通过诱导PUM凝聚物来拯救基因组的不稳定性.
主要成果:
- 通过核化相隔PUM凝聚物 (NP体),NORAD可以竞争性地抑制PUM蛋白.
- 多价PUM-NORAD和PUM-PUM相互作用使NORAD能够隔离大量的PUM.
- 干扰NORAD驱动的阶段分离导致PUM过度活跃和基因组不稳定.
- 诱导PUM凝聚物形成的合成RNA可以挽救基因组的不稳定性.
结论:
- 由RNA驱动的相分离是IncRNA介导的RBP调节的一个关键机制.
- NORAD使用相分离来控制PUM活动并保持基因组稳定性.
- 阶段分离是lncRNAs的一个关键调节机制,由于重复的序列元素而可能广泛传播.
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