title: Defining the functional determinants for RNA surveillance by RIG-I.
abstract: 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kohlway
authors.forename: Dahai
authors.initials: D
authors.lastname: Luo
authors.forename: David C
authors.initials: DC
authors.lastname: Rawling
authors.forename: Steve C
authors.initials: SC
authors.lastname: Ding
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Pyle
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D020365:RNA Helicases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000244:Adenosine Diphosphate; D012313:RNA; D020365:RNA Helicases
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