title: The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response.
abstract: RIG-I, a virus sensor that triggers innate antiviral response, is a DExD/H box RNA helicase bearing structural similarity with Dicer, an RNase III-type nuclease that mediates RNA interference. Dicer requires double-stranded RNA-binding protein partners, such as PACT, for optimal activity. Here we show that PACT physically binds to the C-terminal repression domain of RIG-I and potently stimulates RIG-I-induced type I interferon production. PACT potentiates the activation of RIG-I by poly(I:C) of intermediate length. PACT also cooperates with RIG-I to sustain the activation of antiviral defense. Depletion of PACT substantially attenuates viral induction of interferons. The activation of RIG-I by PACT does not require double-stranded RNA-dependent protein kinase or Dicer, but is mediated by a direct interaction that leads to stimulation of its ATPase activity. Our findings reveal PACT as an important component in initiating and sustaining the RIG-I-dependent antiviral response.
authors.affiliation: Department of Biochemistry and State Key Laboratory for Liver Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Kin-Hang
authors.initials: KH
authors.lastname: Kok
authors.forename: Pak-Yin
authors.initials: PY
authors.lastname: Lui
authors.forename: Ming-Him James
authors.initials: MH
authors.lastname: Ng
authors.forename: Kam-Leung
authors.initials: KL
authors.lastname: Siu
authors.forename: Shannon Wing Ngor
authors.initials: SW
authors.lastname: Au
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Jin
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011070:Poly I-C / Q000276:immunology; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000502:physiology; D014709:Vero Cells; D014780:Viruses / Q000276:immunology* / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism / Q000502:physiology
chemical_list: D007370:Interferon Type I; C104647:PRKRA protein, human; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D019892:eIF-2 Kinase; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C