Protein condensates can evade autophagic degradation under stress or pathological conditions. However, the underlying mechanisms are unclear. Here, we demonstrate that RNAs switch the fate of condensates in Caenorhabditis elegans. PGL granules undergo autophagic degradation in embryos laid under normal conditions and accumulate in embryos laid under heat stress conditions to confer stress adaptation. In heat-stressed embryos, mRNAs and RNA control factors partition into PGL granules. Depleting proteins involved in mRNA biogenesis and stability suppresses PGL granule accumulation and triggers their autophagic degradation, while loss of activity of proteins involved in RNA turnover facilitates accumulation. RNAs facilitate LLPS of PGL granules, enhance their liquidity, and also inhibit recruitment of the gelation-promoting scaffold protein EPG-2 to PGL granules. Thus, RNAs are important for controlling the susceptibility of phase-separated protein condensates to autophagic degradation. Our work provides insights into the accumulation of ribonucleoprotein aggregates associated with the pathogenesis of various diseases.

中文翻译：

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RNA募集将蛋白质凝聚物的命运从自噬降解转变为积累

蛋白质缩合物可以在应激或病理条件下逃避自噬降解。然而，其根本机制尚不清楚。在这里，我们证明 RNA 改变了秀丽隐杆线虫中冷凝物的命运。 PGL颗粒在正常条件下产下的胚胎中经历自噬降解，并在热应激条件下产下的胚胎中积累以赋予应激适应能力。在热应激胚胎中，mRNA 和 RNA 控制因子分配到 PGL 颗粒中。消耗与 mRNA 生物发生和稳定性相关的蛋白质会抑制 PGL 颗粒的积累并引发其自噬降解，而与 RNA 周转相关的蛋白质活性的丧失则会促进积累。 RNA 促进 PGL 颗粒的 LLPS，增强其流动性，并且还抑制促凝胶支架蛋白 EPG-2 向 PGL 颗粒的募集。因此，RNA 对于控制相分离蛋白质凝聚物对自噬降解的敏感性非常重要。我们的工作提供了对与各种疾病发病机制相关的核糖核蛋白聚集体积累的见解。