title: DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling.
abstract: RIG-I-Like Receptors (RLRs) sense cytosolic viral RNA to transiently activate type I IFN production. Here, we report that a type I IFN inducible DExD/H helicase, DDX24, exerts a negative-regulatory effect on RLR function. Expression of DDX24 specifically suppressed RLR activity, while DDX24 loss, which caused embryonic lethality, augmented cytosolic RNA-mediated innate signaling and facilitated RNA virus replication. DDX24 preferentially bound to RNA rather than DNA species and influenced signaling by associating with adaptor proteins FADD and RIP1. These events preferentially impeded IRF7 activity, an essential transcription factor for type I IFN production. Our data provide a new function for DDX24 and help explain innate immune gene regulation, mechanisms that may additionally provide insight into the causes of inflammatory disease.
authors.affiliation: Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ma
authors.forename: Robert
authors.initials: R
authors.lastname: Moore
authors.forename: Xiangxi
authors.initials: X
authors.lastname: Xu
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000276:immunology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D054243:Vesicular Stomatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*
chemical_list: C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D020690:GTPase-Activating Proteins; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse; D012367:RNA, Viral; C490620:Ralbp1 protein, mouse; C485879:Ddx24 protein, mouse; D053487:DEAD-box RNA Helicases