瑞士苏黎世联邦理工学院Karsten Weis小组近日取得一项新成果。他们探明了ATP酶DEAD-box是细胞器相分离的全局调节器。2019年8月22日，《自然》在线发表了这项成果。

研究人员揭示了高度丰富的RNA依赖性DEAD-box ATP酶（DDXs）家族成员是原核生物和真核生物中含有RNA细胞器进行相分离的调节器。利用体外重组和体内实验，他们证明DDX促进结合了ATP的细胞器的相分离，而ATP水解诱导分区转换和RNA的释放。无膜细胞器调节的这种机制揭示了从细菌到人类保守的细胞组成规律。此外，研究人员还发现DDX控制进入和离开相分离细胞器的RNA通量，因此提出了动态细胞网络的假设即DDX控制分区为细胞调控多种RNA成熟过程提供了时间和空间的生化反应中心，这种动态细胞网络可以调节核糖核蛋白颗粒的组成和命运。

近来，蛋白质和核酸经历液-液相分离的能力已成为一种重要的分子原理，即细胞如何快速和可逆地将其组分区分为无膜细胞器，如核仁，加工体或应激颗粒。如何控制这些细胞器的组装和更新，以及这些生物大分子如何选择性地募集或释放的知识知之甚少。

附：英文原文

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

Author: Maria Hondele, Ruchika Sachdev, Stephanie Heinrich, Juan Wang, Pascal Vallotton, Beatriz M. A. Fontoura, Karsten Weis

Issue&Volume: 2019-08-21

Abstract: The ability of proteins and nucleic acids to undergo liquidliquid 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. 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) 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.

DOI: 10.1038/s41586-019-1502-y

Source: https://www.nature.com/articles/s41586-019-1502-y