title: 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 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Rawling
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, United States.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Fitzgerald
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States.|Department of Chemistry, Howard Hughes Medical Institute, Yale University, New Haven, United States.
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Pyle
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007113:Immunity, Innate; D011485:Protein Binding; D012367:RNA, Viral / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: D012367:RNA, Viral; D011971:Receptors, Immunologic; D000255:Adenosine Triphosphate; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: RIG-I like receptor; RNA helicase; antiviral signaling; biochemistry; immunology; innate immunity; none