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DEAD-box ATPases are global regulators of phase-separated organelles

机译：DEAD-box ATPases是相分离细胞器的全局调节剂

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摘要

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.
机译：蛋白质和核酸经历液-液相分离的能力最近已成为一种重要的分子原理，表明细胞如何快速和可逆地将其成分分隔为无膜细胞器，例如核仁，加工体或应激颗粒（1,2 ）。人们对如何控制这些细胞器的组装和周转以及如何选择性地募集或释放这些生物凝结物知之甚少。在这里，我们显示，RNA依赖的DEAD-box ATPases（DDXs）（3）的庞大且高度丰富的家族成员是原核生物和真核生物中包含RNA的相分离细胞器的调节剂。使用体外重构和体内实验，我们证明DDXs以其ATP结合形式促进相分离，而ATP水解诱导隔室更新和RNA释放。这种无膜细胞器调节的机制揭示了从细菌到人类保守的细胞组织原理。此外，我们表明DDXs控制RNA流入和流出相分离的细胞器，因此建议动态，DDX控制的隔室的细胞网络建立生化反应中心，为细胞提供各种RNA加工步骤的时空控制可以调节核糖核蛋白颗粒的组成和命运。

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