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

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Abstract

Retinoic acid-inducible gene I (RIG-I) initiates a rapid innate immune response upon detection and binding to viral 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.

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David C Rawling

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Megan E Fitzgerald

Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Anna Marie Pyle

Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States

For correspondence
anna.pyle@yale.edu

Competing interests
The authors declare that no competing interests exist.

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