RIG-I
RIG-I (retinoic acid-inducible gene I) is a cytosolic pattern recognition receptor (PRR) that can mediate induction of a type-I interferon (IFN1) response. RIG-I is an essential molecule in the innate immune system for recognizing cells that have been infected with a virus. These viruses can include West Nile virus, Japanese Encephalitis virus, influenza A, Sendai virus, flavivirus, and coronaviruses.
RIG-I is an ATP-dependent DExD/H box RNA helicase that is activated by immunostimulatory RNAs from viruses as well as RNAs of other origins. RIG-I recognizes short double-stranded RNA (dsRNA) in the cytosol with a 5' tri- or di-phosphate end or a 5' 7-methyl guanosine (m7G) cap (cap-0), but not RNA with a 5' m7G cap having a ribose 2′-O-methyl modification (cap-1). These are often generated during a viral infection but can also be host-derived. Once activated by the dsRNA, the N-terminus caspase activation and recruitment domains (CARDs) migrate and bind with CARDs attached to mitochondrial antiviral signaling protein (MAVS) to activate the signaling pathway for IFN1.
Type-I IFNs have three main functions: to limit the virus from spreading to nearby cells, promote an innate immune response, including inflammatory responses, and help activate the adaptive immune system. Other studies have shown that in different microenvironments, such as in cancerous cells, RIG-I has more functions other than viral recognition. RIG-I orthologs are found in mammals, geese, ducks, some fish, and some reptiles. RIG-I is in most cells, including various innate immune system cells, and is usually in an inactive state. Knockout mice that have been designed to have a deleted or non-functioning RIG-I gene are not healthy and typically die embryonically. If they survive, the mice have serious developmental dysfunction. The stimulator of interferon genes STING antagonizes RIG-I by binding its N-terminus, probably as to avoid overactivation of RIG-I signaling and the associated autoimmunity.