Retinoic acid-inducible gene-I (RIG-I) is a pattern recognition receptor (PRR) that can recognise RNA viruses in the cytosol. Following the recognition of viral RNA, RIG-I interacts with mitochondrial antiviral-signalling protein (MAVS), located on the surface of mitochondria, to initiate signalling that leads to the production of type 1 interferon and proinflammatory cytokines. Recently, RIG-I foci have been observed in the cytoplasm long after (1-3 days) RNA virus infection, suggesting that RIG-I has functions beyond early virus sensing.
To investigate the role of RIG-I beyond the initial recognition of viral RNA, murine macrophages were stimulated with non-specific ligands for RIG-I that stimulate an immune response (lipopolysaccharide (LPS) or Polyinosinic:polycytidylic acid (poly I:C)). We observed that RIG-I-containing condensates formed in the cytoplasm, which were dynamic and diverse in their components. Approximately half of these RIG-I-containing condensates were Ras-GTPase-activating protein SH3 domain binding protein (G3BP)-containing stress granules. Importantly, we demonstrate that RIG-I has a critical role in the formation of these biomolecular condensates as immune cells deficient in RIG-I failed to form G3BP1+ stress granules. These results suggest that RIG-I contributes to the formation or maintenance of biomolecular condensates in response to inflammation. These findings indicate that during inflammation, RIG-I binds endogenous RNA to initiate the formation of biomolecular condensates.