DEAD-box ATPases are global regulators of phase-separated organelles
DEAD-box ATPases are global regulators of phase-separated organelles
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DOI：
10.1038/s41586-019-1502-y
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发表时间：
2019-09-05
期刊：
影响因子：
64.8
通讯作者：
Weis, Karsten
中科院分区：
文献类型：
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作者：
Hondele, Maria;Sachdev, Ruchika;Weis, Karsten
蛋白质和核酸经历液-液相分离的能力最近已经成为细胞如何快速和可逆地将其组分区室化为无膜细胞器如核仁、加工体或应激颗粒的重要分子原理（1，2）。这些细胞器的组装和周转是如何控制的，以及这些生物冷凝物如何选择性地招募或释放成分，目前还知之甚少。在这里，我们发现，RNA依赖性死亡盒ATP酶（DDXs）（3）的大家族成员是原核生物和真核生物中含RNA相分离细胞器的调节剂。使用体外重建和体内实验，我们证明，DDXs促进相分离在其ATP结合的形式，而ATP水解诱导室营业额和释放的RNA。这种无膜细胞器调节机制揭示了从细菌到人类的细胞组织原理。此外，我们表明，DDXs控制RNA流量进出相分离的细胞器，从而提出，一个动态的细胞网络，DDX控制的隔间建立生化反应中心，为细胞提供空间和时间控制的各种RNA加工步骤，这可以调节核糖核蛋白颗粒的组成和命运。
The ability of proteins and nucleic acids to undergo liquid-liquid phase separation has recently emerged as an important molecular principle of how cells rapidly and reversibly compartmentalize their components into membrane-less organelles such as the nucleolus, processing bodies or stress granules(1,2). How the assembly and turnover of these organelles are controlled, and how these biological condensates selectively recruit or release components are poorly understood. Here we show that members of the large and highly abundant family of RNA-dependent DEAD-box ATPases (DDXs)(3) are regulators of RNA-containing phase-separated organelles in prokaryotes and eukaryotes. Using in vitro reconstitution and in vivo experiments, we demonstrate that DDXs promote phase separation in their ATP-bound form, whereas ATP hydrolysis induces compartment turnover and release of RNA. This mechanism of membrane-less organelle regulation reveals a principle of cellular organization that is conserved from bacteria to humans. Furthermore, we show that DDXs control RNA flux into and out of phase-separated organelles, and thus propose that a cellular network of dynamic, DDX-controlled compartments establishes biochemical reaction centres that provide cells with spatial and temporal control of various RNA-processing steps, which could regulate the composition and fate of ribonucleoprotein particles.