Retinoic acid-inducible gene I (RIG-I) (RIG-I)

Retinoic acid-inducible gene I (RIG-I), also known as DDX58, is a key cytosolic pattern recognition receptor (PRR) that plays a fundamental role in the innate immune system's detection of viral infections (UniProt: O95786). It is an ATP-dependent RNA helicase that recognizes short double-stranded RNA (dsRNA) with 5'-triphosphate or 5'-diphosphate ends, which are typically absent in host cytosolic RNA (PubMed: 21508924). Upon ligand recognition, RIG-I undergoes a conformational shift that allows its caspase activation and recruitment domains (CARDs) to interact with the Mitochondrial Antiviral-Signaling protein (MAVS) on the outer mitochondrial membrane. This interaction initiates a signaling cascade involving TBK1 and IKKε, leading to the activation of IRF3 and NF-κB, which drive the expression of type I interferons (IFN-α/β) and other pro-inflammatory cytokines (PubMed: 24119829). In the context of oncology, RIG-I agonists are being investigated as immunotherapeutic agents to stimulate the tumor microenvironment and enhance anti-tumor T-cell responses (PubMed: 29463566). Therapeutic development focuses on small molecules and synthetic RNA ligands that can selectively activate RIG-I to treat viral infections like Hepatitis B or various solid tumors (ClinicalTrials.gov: NCT03065023).

Other names

DDX58DEAD-box helicase 58Retinoic acid-inducible gene 1 proteinRIG-I-like receptor

RIG-I agonists function by mimicking viral RNA structures, binding to the C-terminal domain and helicase domain of the RIG-I protein. This binding triggers ATP hydrolysis and a structural transition from an auto-inhibited state to an active signaling state, enabling the N-terminal CARD domains to interact with MAVS and initiate the production of type I interferons (PubMed: 21508924, 28439030).