G3BP1 is a tunable switch that triggers phase separation to assemble stress granules
| Autor: | Peipei Zhang, Yuxin Li, Jiyang Yu, Regina-Maria Kolaitis, Jinjun Wu, Peiguo Yang, Cécile Mathieu, Ugur Yurtsever, Qingfei Pan, Tanja Mittag, James Messing, Hong Joo Kim, Erik W. Martin, J. Paul Taylor, Zemin Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Molecular switch
0303 health sciences Granule (cell biology) RNA Cooperativity Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Stress granule Cytoplasm Interaction network Biophysics 030217 neurology & neurosurgery 030304 developmental biology Ribonucleoprotein |
| Zdroj: | Cell |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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