TRIM25 predominately associates with anti-viral stress granules

Zehua Shang, Sitao Zhang, Jinrui Wang, Lili Zhou, Xinyue Zhang, Daniel D. Billadeau, Peiguo Yang, Lingqiang Zhang, Fangfang Zhou, Peng Bai () and Da Jia ()
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Zehua Shang: Sichuan University
Sitao Zhang: Sichuan University
Jinrui Wang: Sichuan University
Lili Zhou: Soochow University
Xinyue Zhang: Sichuan University
Daniel D. Billadeau: Mayo Clinic
Peiguo Yang: Westlake University
Lingqiang Zhang: Beijing Institute of Lifeomics
Fangfang Zhou: Soochow University
Peng Bai: Sichuan University
Da Jia: Sichuan University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48596-4

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