RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation
By Jordina Guillén-Boixet, Andrii Kopach, Alex S. Holehouse, Sina Wittmann, Marcus Jahnel, Raimund Schlüßler, Kyoohyun Kim, I. R. Trussina, Jie Wang, Daniel Matějů and 13 more. Cell, 2020
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Summary 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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/01ef06e2367e8cc42cc06eb6ef146a00456a14cc
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Citations in the corpus
- Competing protein-RNA interaction networks control multiphase intracellular organization (2020, positive): “Instead, along with two accompanying papers from the Alberti and Taylor labs (Guillén-Boixet et al., 2020; Yang et al., 2020), we uncover a modulatory role for IDRs in tuning the RNA-binding capacity of the associated protein complex and its ability to induce RNP condensation.”