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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / immunology*
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Fas-Associated Death Domain Protein / genetics
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Fas-Associated Death Domain Protein / immunology
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / immunology
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Immunity, Innate*
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Interferon Regulatory Factor-7 / genetics
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Interferon Regulatory Factor-7 / immunology
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Interferon Type I / genetics
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Interferon Type I / immunology
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Mice
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Mice, Knockout
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RNA, Viral / genetics
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RNA, Viral / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Vesicular Stomatitis / genetics
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Vesicular Stomatitis / immunology*
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Vesicular Stomatitis / pathology
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Vesicular stomatitis Indiana virus / genetics
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Vesicular stomatitis Indiana virus / immunology*
Substances
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Fadd protein, mouse
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Fas-Associated Death Domain Protein
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GTPase-Activating Proteins
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Interferon Regulatory Factor-7
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Interferon Type I
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Irf7 protein, mouse
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RNA, Viral
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Ralbp1 protein, mouse
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Ddx24 protein, mouse
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DEAD-box RNA Helicases