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 |
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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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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.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1003721</identifier><identifier>PMID: 24204270</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PLoS pathogens, 2013-10, Vol.9 (10), p.e1003721-e1003721</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Ma et al 2013 Ma et al</rights><rights>2013 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Ma Z, Moore R, Xu X, Barber GN (2013) DDX24 Negatively Regulates Cytosolic RNA-Mediated Innate Immune Signaling. 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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.</description><subject>Animals</subject><subject>Cellular signal transduction</subject><subject>DEAD-box RNA Helicases - genetics</subject><subject>DEAD-box RNA Helicases - immunology</subject><subject>Fas-Associated Death Domain Protein - genetics</subject><subject>Fas-Associated Death Domain Protein - immunology</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>GTPase-Activating Proteins - genetics</subject><subject>GTPase-Activating Proteins - immunology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity, Innate</subject><subject>Interferon</subject><subject>Interferon Regulatory Factor-7 - genetics</subject><subject>Interferon Regulatory Factor-7 - immunology</subject><subject>Interferon Type I - genetics</subject><subject>Interferon Type I - immunology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microbiology</subject><subject>Physiological aspects</subject><subject>RNA sequencing</subject><subject>RNA, Viral - genetics</subject><subject>RNA, Viral - immunology</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>Vesicular Stomatitis - genetics</subject><subject>Vesicular Stomatitis - immunology</subject><subject>Vesicular Stomatitis - pathology</subject><subject>Vesicular stomatitis Indiana virus - genetics</subject><subject>Vesicular stomatitis Indiana virus - immunology</subject><subject>Viral infections</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkk1v1DAQhiMEou3CP0AQiQscsvgrcXxBWrV8rFQVqYDEzXJsJ3jl2Fs7qdh_X4dNq0bignywNX7mndfjybJXEKwhpvDDzo_BCbve78WwhgBgiuCT7BSWJS4opuTpo_NJdhbjDgACMayeZyeIIEAQBafZ9uLiFyK5050YzK22hzzobrRi0DGXh8FHb43Mr682Ra-VSWGVG-fSnpu-H53Oo-mSC-O6F9mzVtioX877Kvv5-dOP86_F5bcv2_PNZSErjIeCKE2ZALUkTCqqKoEIhUi1CMIGMVoxTCAqSyU0qFTVYEEBg23bMkUFrSnCq-zNUXdvfeRzFyKHpKwZTipVIrZHQnmx4_tgehEO3AvD_wZ86LgIg5FW86aBCtUYVKKlRJaoYVAxhSQrIQNYtUnr41xtbFIHpHZDEHYhurxx5jfv_C3HNSQ1ncy8mwWCvxl1HHhvotTWCqf9OPkm6dUlTuVW2dsj2olkzbjWJ0U54XyDkyFSloQkav0PKi2leyO9061J8UXC-0VCYgb9Z-jEGCPffr_-D_ZqyZIjK4OPMej2oSsQ8GlE7z-HTyPK5xFNaa8fd_Qh6X4m8R1vLuEJ</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Ma, Zhe</creator><creator>Moore, Robert</creator><creator>Xu, Xiangxi</creator><creator>Barber, Glen N</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131001</creationdate><title>DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling</title><author>Ma, Zhe ; 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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