General information on RIG-I Recombinant Human Retinoic acid-inducible gene I protein
Retinoic acid-inducible gene I (RIG-I) is a member of a family of cytosolic RNA helicases known as RIG-I-like receptors (RLR). RLR also includes MDA5 (melanoma differentiation-associated protein 5) and LGP2 (Laboratory of genetics physiology 2). This family of proteins plays a vital role in antiviral innate immunity by responding to viral nucleic acids and activating downstream signaling pathways. In turn, these pathways induce the expression of type I interferon (IFN) in a TLR-independent manner (TLR, toll-like receptors), one of the most important effectors of innate immunity. RIG-I is a 925 amino acid protein encoded by the DDX58 gene in humans and it consists of a helical ATP-dependent DExD/H box RNA helicase. On the C-terminus, RIG-I has a repressor domain (RD) responsible for binding the target RNA, while on the N-terminus, it contains two caspase activation and recruitment domains (CARDs) responsible for interacting with mitochondrial antiviral signaling protein (MAVS). RIG-I is also known as a virus sensor and, after binding to double-stranded viral RNA (dsRNA) or 5’-triphosphate single-stranded viral RNA (ssRNA), it changes into an open conformation, translocating to the mitochondria where it interacts with MAVS via the CARDs signaling domains. This ability to sense the presence of viral RNA is invaluable, as viruses can highjack the host’s replication machinery to replicate themselves and amplify the infection. Thus, RIG-I is one of many molecules providing the first line of defense against dangerous viral pathogens. To avoid excess IFN production, RIG-I signaling pathways are strictly regulated by other cellular mechanisms. LGP2 is one of the molecules that actively participates in the regulation of RIG-I by competitively sequestrating dsRNA. However, other studies also show that LPG2 might also enhance RIG-I signaling in certain viral infections. Additionally, RIG-I signaling can also be regulated by specific post-translational modifications of the protein such as ubiquitylation, phosphorylation, and SUMOylation. In addition to its role as a virus sensor, RIG-I has been shown to participate in several other biological processes including inflammation, cell proliferation, apoptosis, and even senescence. For these reasons, RIG-I remains an important reagent for both basic and medical research.