RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation.
Cell
; 181(2): 346-361.e17, 2020 04 16.
Article
em En
| MEDLINE
| ID: mdl-32302572
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleoproteínas
/
DNA Helicases
/
RNA Helicases
/
Grânulos Citoplasmáticos
/
Proteínas com Motivo de Reconhecimento de RNA
/
Proteínas de Ligação a Poli-ADP-Ribose
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article