The C-Terminal Regulatory Domain Is the RNA 5′-Triphosphate Sensor of RIG-I

Tags

Top Highlights

• Upon recognition of cytosolic viral RNA, RIG-I and MDA5 bind to the adaptor protein IPS-1 (also known as CARDIF, MAVS, or VISA

• Recent results show that RIG-I distinguishes viral RNA from the vast amount and variety of cellular RNAs by recognizing 5′-triphosphates, a modification that arises from RNA synthesis by many viruses but is not found on normal capped or processed cellular RNA

• MDA5 activation can be stimulated by the dsRNA analog polyinosine-polycytidylic acid (poly[I:C]), but the precise determinants of viral RNA detected by MDA5 remain elusive

• LGP2 interferes with the RIG-I-dependent stimulation of interferon production, suggesting it might have a regulatory role

• RIG-I and MDA5 consist of two N-terminal caspase activation and recruitment domains (CARDs), a central SF2 type DECH box ATPase domain, and a C-terminal extension of little sequence homology to other proteins

• LGP2 lacks the two N-terminal CARDs but contains the DECH box domain, as well as a C-terminal extension.