Nature Communications (May 2024)

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,
  • Da Jia

DOI
https://doi.org/10.1038/s41467-024-48596-4
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 17

Abstract

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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.