2020年4月16日 · 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.

2020年4月16日 · Biophysical studies revealed details of how G3BP1 functions as a molecular switch that triggers RNA-dependent LLPS. Importantly, 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.

2022年1月5日 · Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid …

2021年6月25日 · This rise in cytoplasmic mRNA triggers multicomponent liquid-liquid phase separation (LLPS) with RNA-binding proteins, creating a condensed liquid compartment that remains in dynamic equilibrium with, yet distinct from, the surrounding cytosol (3–5).

2021年11月15日 · By showing a G3BP1‐mediated regulation of cGAS LLPS, our study provides important insights to further understand the precise regulation of cGAS activation by phase separation. Using high‐resolution microscopy, we showed that the particle‐like morphological characteristics of cGAS in cytoplasm was markedly weakened in G3BP1 −/− cells ...

2024年12月1日 · Ras-GTPase-activating protein-binding protein 1 (G3BP1) is a core component and crucial regulatory switch in stress granules (SGs). When the concentration of free RNA within cells increases, it can trigger RNA-dependent liquid-liquid phase separation (LLPS) with G3BP1 as the core, thereby forming SGs that affect cell survival or death.

Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) is a multi-functional protein that is best known for its role in the assembly and dynamics of stress granules. Recent studies have highlighted that G3BP1 also has other functions related to RNA metabolism.

TRIM21 catalyzes K63-linked ubiquitination of the SG core protein, G3BP1 (G3BP stress granule assembly factor 1), and G3BP1 ubiquitination can effectively inhibit LLPS, in vitro. Recent reports suggested the involvement of macroautophagy/autophagy, as a stress response pathway, in the regulation of SG homeostasis.

2023年4月26日 · Mechanically, DNA-induced liquid-liquid phase separation (LLPS) of N protein competitively binds with G3BP1, a co-factor of cGAS, resulting in the disruption of cGAS-G3BP1 complex...

2024年12月20日 · Ras GTPase -activating protein -binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of SGs 17. Recent studies have identified lncRNAs within phase separation bodies 18 -20, where they influence disease development and progression by modulating LLPS 21 -23. This discovery