DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling

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, wh...

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Veröffentlicht in:PLoS pathogens 2013-10, Vol.9 (10), p.e1003721-e1003721
Hauptverfasser: Ma, Zhe, Moore, Robert, Xu, Xiangxi, Barber, Glen N
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container_title PLoS pathogens
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creator Ma, Zhe
Moore, Robert
Xu, Xiangxi
Barber, Glen N
description 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.
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Moore, Robert ; Xu, Xiangxi ; Barber, Glen N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c633t-4de79a08c49cd7d6a24712df211b29769341255dae06d6b3a7091fff9d7a78723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Cellular signal transduction</topic><topic>DEAD-box RNA Helicases - genetics</topic><topic>DEAD-box RNA Helicases - immunology</topic><topic>Fas-Associated Death Domain Protein - genetics</topic><topic>Fas-Associated Death Domain Protein - immunology</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>GTPase-Activating Proteins - genetics</topic><topic>GTPase-Activating Proteins - immunology</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity, Innate</topic><topic>Interferon</topic><topic>Interferon Regulatory Factor-7 - genetics</topic><topic>Interferon Regulatory Factor-7 - immunology</topic><topic>Interferon Type I - genetics</topic><topic>Interferon Type I - immunology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microbiology</topic><topic>Physiological aspects</topic><topic>RNA sequencing</topic><topic>RNA, Viral - genetics</topic><topic>RNA, Viral - immunology</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>Vesicular Stomatitis - genetics</topic><topic>Vesicular Stomatitis - immunology</topic><topic>Vesicular Stomatitis - pathology</topic><topic>Vesicular stomatitis Indiana virus - genetics</topic><topic>Vesicular stomatitis Indiana virus - immunology</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Zhe</creatorcontrib><creatorcontrib>Moore, Robert</creatorcontrib><creatorcontrib>Xu, Xiangxi</creatorcontrib><creatorcontrib>Barber, Glen N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Zhe</au><au>Moore, Robert</au><au>Xu, Xiangxi</au><au>Barber, Glen N</au><au>Heise, Mark T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>9</volume><issue>10</issue><spage>e1003721</spage><epage>e1003721</epage><pages>e1003721-e1003721</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24204270</pmid><doi>10.1371/journal.ppat.1003721</doi><oa>free_for_read</oa></addata></record>
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subjects Animals
Cellular signal transduction
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - immunology
Fas-Associated Death Domain Protein - genetics
Fas-Associated Death Domain Protein - immunology
Genes
Genetic aspects
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - immunology
Immune response
Immune system
Immunity, Innate
Interferon
Interferon Regulatory Factor-7 - genetics
Interferon Regulatory Factor-7 - immunology
Interferon Type I - genetics
Interferon Type I - immunology
Mice
Mice, Knockout
Microbiology
Physiological aspects
RNA sequencing
RNA, Viral - genetics
RNA, Viral - immunology
Signal Transduction - genetics
Signal Transduction - immunology
Vesicular Stomatitis - genetics
Vesicular Stomatitis - immunology
Vesicular Stomatitis - pathology
Vesicular stomatitis Indiana virus - genetics
Vesicular stomatitis Indiana virus - immunology
Viral infections
title DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling
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