RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress 
Granule Assembly by Condensation.

Guillén-Boixet, Jordina; Kopach, Andrii; Holehouse, Alex S; Wittmann, Sina; Jahnel, Marcus; Schlüßler, Raimund; Kim, Kyoohyun; Trussina, Irmela; Wang, Jie; Mateju, Daniel; Poser, Ina; Maharana, Shovamayee; Ruer-Gruß, Martine; Richter, Doris; Zhang, Xiaojie; Chang, Young-Tae; Guck, Jochen; Honigmann, Alf; Mahamid, Julia; Hyman, Anthony; Pappu, Rohit V; Alberti, Simon; Franzmann, Titus

doi:10.1016/j.cell.2020.03.049

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RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation.

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/persons/resource/persons231686

Guillén-Boixet, Jordina
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219330

Kopach, Andrii
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons232169

Wittmann, Sina
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons204000

Jahnel, Marcus
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219750

Trussina, Irmela
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons222397

Wang, Jie
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219433

Mateju, Daniel
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219545

Poser, Ina
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219414

Maharana, Shovamayee
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219595

Ruer-Gruß, Martine
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219580

Richter, Doris
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons40292

Honigmann, Alf
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons104436

Mahamid, Julia
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219253

Hyman, Anthony
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons218962

Alberti, Simon
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219166

Franzmann, Titus
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Guillén-Boixet, J., Kopach, A., Holehouse, A. S., Wittmann, S., Jahnel, M., Schlüßler, R., et al. (2020). RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation. Cell, 181(2), 346-361. doi:10.1016/j.cell.2020.03.049.

Cite as: https://hdl.handle.net/21.11116/0000-0008-A342-5

Abstract

Stressed cells shut down translation, release mRNA molecules from polysomes, and form stress granules (SGs) via a network of interactions that involve G3BP. Here we focus on the mechanistic underpinnings of SG assembly. We show that, under non-stress conditions, G3BP adopts a compact auto-inhibited state stabilized by electrostatic intramolecular interactions between the intrinsically disordered acidic tracts and the positively charged arginine-rich region. Upon release from polysomes, unfolded mRNAs outcompete G3BP auto-inhibitory interactions, engendering a conformational transition that facilitates clustering of G3BP through protein-RNA interactions. Subsequent physical crosslinking of G3BP clusters drives RNA molecules into networked RNA/protein condensates. We show that G3BP condensates impede RNA entanglement and recruit additional client proteins that promote SG maturation or induce a liquid-to-solid transition that may underlie disease. We propose that condensation coupled to conformational rearrangements and heterotypic multivalent interactions may be a general principle underlying RNP granule assembly.