PDF(Pubmed)
Abstract：
Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role in the antiviral process, owing to their potent translational repressive effects and ability to trigger signal transduction; however, it is poorly understood how these antiviral SGs differ from SGs induced by other environmental stressors. Here we identify that TRIM25, a known driver of the ubiquitination-dependent antiviral innate immune response, is a potent and critical marker of the antiviral SGs. TRIM25 undergoes liquid-liquid phase separation (LLPS) and co-condenses with the SG core protein G3BP1 in a dsRNA-dependent manner. The co-condensation of TRIM25 and G3BP1 results in a significant enhancement of TRIM25\'s ubiquitination activity towards multiple antiviral proteins, which are mainly located in SGs. This co-condensation is critical in activating the RIG-I signaling pathway, thus restraining RNA virus infection. Our studies provide a conceptual framework for better understanding the heterogeneity of stress granule components and their response to distinct environmental stressors.
摘要：
应激颗粒(SGs)是由各种环境应激源诱导的，导致它们的组成和功能异质性。SGs在抗病毒过程中起着至关重要的作用，由于其强大的翻译抑制作用和触发信号转导的能力;然而，我们对这些抗病毒SGs与其他环境应激源诱导的SGs有何不同知之甚少。在这里，我们发现TRIM25是泛素化依赖性抗病毒先天免疫反应的已知驱动因素，是抗病毒SGs的有效和关键标记。TRIM25经历液-液相分离(LLPS)并以dsRNA依赖性方式与SG核心蛋白G3BP1共缩合。TRIM25和G3BP1的共缩合导致TRIM25对多种抗病毒蛋白的泛素化活性显著增强，主要位于SGS。这种共缩合在激活RIG-I信号通路中至关重要，从而抑制RNA病毒感染。我们的研究为更好地理解应激颗粒成分的异质性及其对不同环境压力源的反应提供了一个概念框架。
