Retinoic acid-inducible gene i-like receptors

Family of cytosolic (cytoplasmic) pattern recognition receptors(PRRs) that primarily recognize viral RNA in the cytoplasm

The family of cytoplasmic pattern recognition receptors (PRRs) includes:

• RIG-1: the cytosolic helicases retinoic acid-inducible gene I (RIG-I)
• MDA-5: the melanoma differentiation-associated gene 5 (MDA-5)
• LGP-2: the laboratory of genetics and physiology 2 (LGP-2).

The "retinoic acid-inducible gene I-like receptors" recognize viral RNA in the cytoplasm as cytosolic receptors, in contrast to the membrane-bound PRRs, e.g. Toll-like receptor(Akira S et al. 2006). Studies on animals with corresponding genetic defects for the individual PR receptors have shown that these cytosolic PRRs recognize different viruses (Kato H 2005).

RIG-I receptors recognize single-stranded and double-stranded viral RNA (e.g. influenza A). Various structures of the RNA and a triphosphate group at the 5'-end are decisive for this (Hornung V et al. 2006).

MDA-5 receptors recognize RNA, e.g. of the encephalomyocarditis virus (EMCV) (Takeuchi O et al. 2008).

Both RIG-I and MDA-5 function in an analogous manner. Both have an N-terminal caspase recruitment domain (CARD). In addition, RIG-I has a helicase domain and a C-terminal repressor domain (CR domain). The helicase domain and the CR domain bind to RNA.

The N-terminal CARD is used for signal transduction via CARD interactions. After binding to adapter proteins, the signaling cascade leads via TRADD (tumor necrosis factor receptor type 1-associated DEATH domain) to the translocation of the transcription factors NF-kappaB and ultimately to the induction of type I interferons.

LGP-2: The function of LGP-2 is still unknown. It is possible that LGP-2 binds to RIG-I and exerts an inhibitory function.

1. Akira S et al.(2006) Pathogen recognition and innate immunity. Cell 124: 783-801
2. Yoneyama M et al (2008) Structural mechanism of RNA recognition by the RIG-I-like receptors. Immunity 29: 178-181
3. Kato H et al (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23: 19-28
4. Kato H et al (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101-105
5. Hornung V et al (2006) 5'-triphosphates RNA is the ligand for RIG-I. Science 314: 994-997
6. Takeuchi O et al (2008) MDA5/RIG-I and virus recognition. Curr Opin Immunol 20: 17-22