TY - JOUR
T1 - DEAD-box ATPases are global regulators of phase-separated organelles
AU - Hondele, Maria
AU - Sachdev, Ruchika
AU - Heinrich, Stephanie
AU - Wang, Juan
AU - Vallotton, Pascal
AU - Fontoura, Beatriz M.A.
AU - Weis, Karsten
N1 - Funding Information:
Acknowledgements We would like to thank G. Stojanovski and M. Martinovic for technical assistance. We are grateful to A. Sachs and J. Liphardt for plasmids, S. Jonas, M. Jinek, P. Kimming, E. Dultz, S. Khawaja, C. Weber and M. Zedan for their critical reading of this manuscript, ScopeM and J. Kusch for help with microscopy, M. Linsenmeier and A. Küffner for discussions of image and protein sequence analysis, and members of the Weis laboratory for discussions and comments. M.H. was supported by a Human Frontier Science Program (HFSP) postdoctoral fellowship (LT000914/2015) and an ETH postdoctoral fellowship (FEL-37-14-2). S.H. and M.H. acknowledge support from an EMBO long-term fellowship (ALTF 290-2014, EMBOCOFUND2012, GA-2012-600394 to S.H.; ALTF 870-2014 to M.H.). This work was supported by the Swiss National Science Foundation (SNF 31003A_179275 and 31003A_159731 to K.W.).
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/9/5
Y1 - 2019/9/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071036149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071036149&partnerID=8YFLogxK
U2 - 10.1038/s41586-019-1502-y
DO - 10.1038/s41586-019-1502-y
M3 - Article
C2 - 31435012
AN - SCOPUS:85071036149
SN - 0028-0836
VL - 573
SP - 144
EP - 148
JO - Nature
JF - Nature
IS - 7772
ER -