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EMBO Rep. 2013 Sep;14(9):772-9. doi: 10.1038/embor.2013.108. Epub 2013 Jul 30.

Defining the functional determinants for RNA surveillance by RIG-I.

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1
Department of Molecular Biophysics and Biochemistry.

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.

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PMID:
23897087
PMCID:
PMC3790051
DOI:
10.1038/embor.2013.108
[Indexed for MEDLINE]
Free PMC Article

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