TY - JOUR TI - Establishing the role of ATP for the function of the RIG-I innate immune sensor AU - Rawling, David C AU - Fitzgerald, Megan E AU - Pyle, Anna Marie A2 - Kowalczykowski, Stephen C VL - 4 PY - 2015 DA - 2015/09/15 SP - e09391 C1 - eLife 2015;4:e09391 DO - 10.7554/eLife.09391 UR - https://doi.org/10.7554/eLife.09391 AB - 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. KW - RIG-I like receptor KW - RNA helicase KW - innate immunity KW - antiviral signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -