Topic summary
RIG-I
RIG-I (retinoic acid-inducible gene I), encoded by the gene DDX58 (DEAD box polypeptide 58), is a cytosolicpattern 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, including but not limited to West Nile virus, Japanese Encephalitis virus, influenza A, Sendai virus, flavivirus, and coronaviruses.
RIG-I is an ATP-dependent DExD/H boxRNA helicase activated by specific types of RNA. RIG-I recognizes short double-stranded RNA (dsRNA) in the cytosol with a 5' tri- or di-phosphate end (ppN, pppN) or a 5' 7-methyl guanosine (m7G) cap (cap-0) without a ribose 2′-O-methyl modification at the next unit (cap-0). Such RNAs are often generated during a viral infection but can also be host-derived. For example, RIG-I also plays a role in cancer microenvironments.
Once activated by the dsRNA, RIG-I interacts with MAVS via CARD domains to activate the signaling pathway for IFN1. IFN1s 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.
RIG-I is expressed in most cells, including various innate immune system cells, and is usually in an inactive state. RIG-I orthologs are found in mammals, geese, ducks, some fish, and some reptiles. 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.