Defining the functional determinants for RNA surveillance by RIG-I.
Publication Type:Journal Article
Source:EMBO Rep, Volume 14, Issue 9, p.772-9 (2013)
Keywords:Adenosine Diphosphate, Amino Acid Sequence, Catalytic Domain, HEK293 Cells, Humans, Molecular Docking Simulation, Molecular Sequence Data, Protein Binding, RNA, RNA Helicases
<p>Retinoic acid-inducible gene-I (RIG-I) is an intracellular RNA sensor that activates the innate immune machinery in response to infection by RNA viruses. Here, we report the crystal structure of distinct conformations of a RIG-I:dsRNA complex, which shows that HEL2i-mediated scanning allows RIG-I to sense the length of RNA targets. To understand the implications of HEL2i scanning for catalytic activity and signalling by RIG-I, we examined its ATPase activity when stimulated by duplex RNAs of varying lengths and 5' composition. We identified a minimal RNA duplex that binds one RIG-I molecule, stimulates robust ATPase activity, and elicits a RIG-I-mediated interferon response in cells. Our results reveal that the minimal functional unit of the RIG-I:RNA complex is a monomer that binds at the terminus of a duplex RNA substrate. This behaviour is markedly different from the RIG-I paralog melanoma differentiation-associated gene 5 (MDA5), which forms cooperative filaments. </p>