title: The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response.
abstract: Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to induction of interferons (IFNs) and proinflammatory cytokines, and innate antiviral response. Here we identified the RNA-binding protein Mex3B as a positive regulator of TLR3-mediated signaling by expression cloning screens. Cells from Mex3b(-/-) mice exhibited reduced production of IFN-β in response to the dsRNA analog poly(I:C) but not infection with RNA viruses. Mex3b(-/-) mice injected with poly(I:C) was more resistant to poly(I:C)-induced death. Mex3B was associated with TLR3 in the endosomes. It bound to dsRNA and increased the dsRNA-binding activity of TLR3. Mex3B also promoted the proteolytic processing of TLR3, which is critical for its activation. Mutants of Mex3B lacking its RNA-binding activity inhibited TLR3-mediated IFN-β induction. These findings suggest that Mex3B acts as a coreceptor of TLR3 in innate antiviral response.
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Hubei 430071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Hubei 430071, China.
authors.forename: Su-Yun
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Hubei 430071, China.
authors.forename: Zhe-Fu
authors.initials: ZF
authors.lastname: Huang
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Hubei 430071, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zou
authors.affiliation: Collaborative Innovation Center for Viral Immunology, Medical Research Institute, College of Life Sciences, Wuhan University, Hubei 430072, China.
authors.forename: Bing-Ru
authors.initials: BR
authors.lastname: Yan
authors.affiliation: Collaborative Innovation Center for Viral Immunology, Medical Research Institute, College of Life Sciences, Wuhan University, Hubei 430072, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Luo
authors.affiliation: Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Hubei 430071, China.
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D008297:Male; D018345:Mice, Knockout; D011070:Poly I-C / Q000494:pharmacology; D012328:RNA Viruses / Q000502:physiology; D012330:RNA, Double-Stranded / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D011070:Poly I-C; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D051196:Toll-Like Receptor 3; C000589341:MEX3B protein, mouse; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse
references.citation: Science. 2005 Jul 22;309(5734):581-5
references.pmid: 15961631
references.citation: Immunity. 2010 Mar 26;32(3):305-15
references.pmid: 20346772
references.citation: J Biol Chem. 2005 Nov 18;280(46):38133-45
references.pmid: 16144834
references.citation: Immunity. 2006 Feb;24(2):153-63
references.pmid: 16473828
references.citation: EMBO J. 2006 Jul 26;25(14):3335-46
references.pmid: 16858407
references.citation: Nucleic Acids Res. 2007;35(4):1289-300
references.pmid: 17267406
references.citation: Science. 2007 Sep 14;317(5844):1522-7
references.pmid: 17872438
references.citation: FASEB J. 2008 Jan;22(1):159-67
references.pmid: 17709607
references.citation: Nat Methods. 2008 Feb;5(2):163-5
references.pmid: 18176569
references.citation: Science. 2008 Apr 18;320(5874):379-81
references.pmid: 18420935
references.citation: J Immunol. 2003 Sep 15;171(6):3154-62
references.pmid: 12960343
references.citation: Science. 1990 Sep 21;249(4975):1431-3
references.pmid: 1698311
references.citation: Immunity. 2008 Aug 15;29(2):182-91
references.pmid: 18701082
references.citation: J Immunol. 2008 Oct 15;181(8):5522-9
references.pmid: 18832709
references.citation: J Biol Chem. 2008 Nov 14;283(46):32131-42
references.pmid: 18779327
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20252-7
references.pmid: 19915141
references.citation: Curr Opin Immunol. 2010 Feb;22(1):20-7
references.pmid: 20060278
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10976-80
references.pmid: 16043704
references.citation: J Biol Chem. 2010 Apr 23;285(17):12543-50
references.pmid: 20200155
references.citation: J Biol Chem. 2010 Nov 19;285(47):36635-44
references.pmid: 20855885
references.citation: Immunity. 2011 May 27;34(5):637-50
references.pmid: 21616434
references.citation: J Exp Med. 2011 Sep 26;208(10):2083-98
references.pmid: 21911422
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9053-8
references.pmid: 22611194
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11770-5
references.pmid: 22745163
references.citation: J Biol Chem. 2012 Sep 21;287(39):32617-29
references.pmid: 22865861
references.citation: J Biol Chem. 2013 Jan 4;288(1):442-54
references.pmid: 23166319
references.citation: J Immunol. 2013 Jan 15;190(2):764-73
references.pmid: 23255358
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5115-20
references.pmid: 23479606
references.citation: Nucleic Acids Res. 2013 Apr;41(7):3986-99
references.pmid: 23408853
references.citation: Science. 2013 Sep 20;341(6152):1390-4
references.pmid: 23989956
references.citation: Trends Biochem Sci. 2013 Oct;38(10):477-9
references.pmid: 23999169
references.citation: Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5646-51
references.pmid: 24706898
references.citation: Development. 2014 May;141(10):2096-107
references.pmid: 24803656
references.citation: J Immunol. 2014 Nov 15;193(10):5208-17
references.pmid: 25305318