G3BP1 is a tunable switch that triggers phase separation to assemble stress granules
By Peiguo Yang, Cécile Mathieu, Regina-Maria Kolaitis, Peipei Zhang, James Messing, Ugur Yurtsever, Zemin Yang, Jinjun Wu, Yuxin Li, Qingfei Pan and 5 more. Cell, 2020
1,130 citations recorded by the source corpus.
Summary The mechanisms underlying ribonucleoprotein (RNP) granule assembly, including the basis for establishing and maintaining RNP granules with distinct composition, are unknown. One prominent type of RNP granule is the stress granule (SG), a dynamic and reversible cytoplasmic assembly formed in eukaryotic cells in response to stress. Here we show that SGs assemble through liquid-liquid phase separation (LLPS) arising from interactions distributed unevenly across a core protein-RNA interaction network. The central node of this network is G3BP1, which functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations. Moreover, we show that interplay between three distinct intrinsically disordered regions (IDRs) in G3BP1 regulates its intrinsic propensity for LLPS, and this is fine-tuned by phosphorylation within the IDRs. Further regulation of SG assembly arises through positive or negative cooperativity by extrinsic G3BP1-binding factors that strengthen or weaken, respectively, the core SG network.
Subfields: Biomaterials, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/15e333a148c75ffc3ed490c861a35f645cdac1af
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
- P. Ivanov
- Paul Anderson
- N. Kedersha
- C. Brangwynne
- Daniel S. W. Lee
- David W. Sanders
- Joshua A. Riback
- Jonathan S. Weissman
Citations in the corpus
- OpenCell: proteome-scale endogenous tagging enables the cartography of human cellular organization (2022, background): “4C) that separate into granules upon stress conditions ( 56 – 59 ).”
- 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.”