Establishing the role of ATP for the function of the RIG-I innate immune sensor
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.
Article and author information
Author details
Reviewing Editor
- Stephen C Kowalczykowski, University of California, Davis, United States
Version history
- Received: June 12, 2015
- Accepted: September 14, 2015
- Accepted Manuscript published: September 15, 2015 (version 1)
- Version of Record published: October 27, 2015 (version 2)
Copyright
© 2015, Rawling et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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