Parker Dylan M, Tauber Devin, Parker Roy
Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO 80309, USA.
Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
Mol Cell. 2025 Feb 6;85(3):571-584.e7. doi: 10.1016/j.molcel.2024.11.012. Epub 2024 Dec 4.
Ribonucleoprotein (RNP) granules are biomolecular condensates requiring RNA and proteins to assemble. Stress granules are RNP granules formed upon increases in non-translating messenger ribonucleoprotein particles (mRNPs) during stress. G3BP1 and G3BP2 proteins are proposed to assemble stress granules through multivalent crosslinking of RNPs. We demonstrate that G3BP1 also has "condensate chaperone" functions, which promote the assembly of stress granules but are dispensable following initial condensation. Following granule formation, G3BP1 is dispensable for the RNA component of granules to persist in vitro and in cells when RNA decondensers are inactivated. These results demonstrate that G3BP1 functions as an "RNA condenser," a protein that promotes intermolecular RNA-RNA interactions stabilizing RNA condensates, leading to RNP granule persistence. Moreover, the stability of RNA-only granules highlights the need for active mechanisms limiting RNP condensate stability and lifetime.
核糖核蛋白（RNP）颗粒是需要RNA和蛋白质组装的生物分子凝聚物。应激颗粒是在应激期间非翻译信使核糖核蛋白颗粒（mRNP）增加时形成的RNP颗粒。有人提出G3BP1和G3BP2蛋白通过RNP的多价交联来组装应激颗粒。我们证明G3BP1还具有“凝聚物伴侣”功能，可促进应激颗粒的组装，但在初始凝聚后是可有可无的。在颗粒形成后，当RNA解凝聚剂失活时，G3BP1对于颗粒的RNA成分在体外和细胞中持续存在是可有可无的。这些结果表明，G3BP1作为一种“RNA凝聚剂”发挥作用，这是一种促进分子间RNA-RNA相互作用以稳定RNA凝聚物从而导致RNP颗粒持续存在的蛋白质。此外，仅RNA颗粒的稳定性凸显了限制RNP凝聚物稳定性和寿命的活性机制的必要性。
