ATP酶DEAD-box調節細胞器的相分離
作者：
小柯機器人發布時間：2019/8/22 14:42:52
瑞士蘇黎世聯邦理工學院Karsten Weis小組近日取得一項新成果。他們探明了ATP酶DEAD-box是細胞器相分離的全局調節器。2019年8月22日，《自然》在線發表了這項成果。
研究人員揭示了高度豐富的RNA依賴性DEAD-box ATP酶（DDXs）家族成員是原核生物和真核生物中含有RNA細胞器進行相分離的調節器。利用體外重組和體內實驗，他們證明DDX促進結合了ATP的細胞器的相分離，而ATP水解誘導分區轉換和RNA的釋放。無膜細胞器調節的這種機制揭示了從細菌到人類保守的細胞組成規律。此外，研究人員還發現DDX控制進入和離開相分離細胞器的RNA通量，因此提出了動態細胞網絡的假設即DDX控制分區為細胞調控多種RNA成熟過程提供了時間和空間的生化反應中心，這種動態細胞網絡可以調節核糖核蛋白顆粒的組成和命運。
近來，蛋白質和核酸經歷液-液相分離的能力已成為一種重要的分子原理，即細胞如何快速和可逆地將其組分區分為無膜細胞器，如核仁，加工體或應激顆粒。如何控制這些細胞器的組裝和更新，以及這些生物大分子如何選擇性地募集或釋放的知識知之甚少。
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