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Elife. 2015 Sep 15;4. pii: e09391. doi: 10.7554/eLife.09391.

Establishing the role of ATP for the function of the RIG-I innate immune sensor.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States.
2
Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, United States.
3
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States.
4
Department of Chemistry, Howard Hughes Medical Institute, Yale University, New Haven, United States.

Abstract

Retinoic acid-inducible gene I (RIG-I) initiates a rapid innate immune response upon detection and binding to viral ribonucleic acid (RNA). This signal activation occurs only when pathogenic RNA is identified, despite the ability of RIG-I to bind endogenous RNA while surveying the cytoplasm. Here we show that ATP binding and hydrolysis by RIG-I play a key role in the identification of viral targets and the activation of signaling. Using biochemical and cell-based assays together with mutagenesis, we show that ATP binding, and not hydrolysis, is required for RIG-I signaling on viral RNA. However, we show that ATP hydrolysis does provide an important function by recycling RIG-I and promoting its dissociation from non-pathogenic RNA. This activity provides a valuable proof-reading mechanism that enhances specificity and prevents an antiviral response upon encounter with host RNA molecules.

KEYWORDS:

RIG-I like receptor; RNA helicase; antiviral signaling; biochemistry; immunology; innate immunity; none

PMID:
26371557
PMCID:
PMC4622095
DOI:
10.7554/eLife.09391
[Indexed for MEDLINE]
Free PMC Article

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