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TRIM25 predominately associates with anti-viral stress granules

Author

Listed:
  • 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)

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.

Suggested Citation

  • Zehua Shang & Sitao Zhang & Jinrui Wang & Lili Zhou & Xinyue Zhang & Daniel D. Billadeau & Peiguo Yang & Lingqiang Zhang & Fangfang Zhou & Peng Bai & Da Jia, 2024. "TRIM25 predominately associates with anti-viral stress granules," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48596-4
    DOI: 10.1038/s41467-024-48596-4
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