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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-? 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-? induction. These findings suggest that Mex3B acts as a coreceptor of TLR3 in innate antiviral response.

SUBMITTER: Yang Y

PROVIDER: S-EPMC4783467 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response.

Yang Yan Y Wang Su-Yun SY Huang Zhe-Fu ZF Zou Hong-Mei HM Yan Bing-Ru BR Luo Wei-Wei WW Wang Yan-Yi YY

Cell research 20160129 3

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 pol ...[more]

PMID: 26823206

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