RIG-I, short for retinoic acid-inducible gene I, is a key cytoplasmic RNA helicase and a major pattern recognition receptor of the innate immune system. It detects nonself RNA as a pathogen-associated molecular pattern (PAMP), and upon activation, signals via the MAVS-IRF-3 axis, leading to the upregulation of antiviral interferons [2,4,5]. It is also involved in various immune-related processes, playing a crucial role in the body's defense against viral infections.

IFI16 knockout cells and p204-deficient mice demonstrated that IFI16 enhances RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also promotes IAV-induced K63-linked polyubiquitination and RIG-I activation, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses [1]. In CD8+ T cells, Rig-I deficiency or inhibition enhanced the tumor-restricting effect of endogenous or adoptively transferred CD8+ T cells, with increased accumulation, survival, and cytotoxicity of tumor-infiltrating CD8+ T cells. Mechanistically, T cell activation-induced RIG-I upregulation restrained STAT5 activation via competitive sequestering of HSP90 [3].

In conclusion, RIG-I is essential for the innate immune response, especially in sensing viral RNAs and initiating antiviral interferon production. The use of gene knockout models, such as in IFI16 knockout cells and p204-deficient mice, as well as Rig-I deficiency in CD8+ T cells, has revealed its role in antiviral immunity and tumor-related immunomodulation, providing insights into potential therapeutic strategies for viral infections and cancer treatment.