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

Maria Hondele, Ruchika Sachdev, Stephanie Heinrich, Juan Wang, Pascal Vallotton, Beatriz M. A. Fontoura and Karsten Weis ()
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Maria Hondele: ETH Zurich
Ruchika Sachdev: ETH Zurich
Stephanie Heinrich: ETH Zurich
Juan Wang: University of Texas Southwestern Medical Center
Pascal Vallotton: ETH Zurich
Beatriz M. A. Fontoura: University of Texas Southwestern Medical Center
Karsten Weis: ETH Zurich

Nature, 2019, vol. 573, issue 7772, 144-148

Abstract: Abstract 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 granules1,2. 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.

Date: 2019
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DOI: 10.1038/s41586-019-1502-y

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