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

被引：46

作者：

Yang, Yan ^{[1
]}

Wang, Su-Yun ^{[1
]}

Huang, Zhe-Fu ^{[1
]}

Zou, Hong-Mei ^{[1
]}

Yan, Bing-Ru ^{[2
]}

Luo, Wei-Wei ^{[2
]}

Wang, Yan-Yi ^{[1
]}

机构：

[1] Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, Wuhan 430071, Hubei, Peoples R China

[2] Wuhan Univ, Coll Life Sci, Med Res Inst, Collaborat Innovat Ctr Viral Immunol, Wuhan 430072, Hubei, Peoples R China

来源：

CELL RESEARCH | 2016年 / 26卷 / 03期

基金：

中国国家自然科学基金;

关键词：

TLR3; Mex3B; proteolytic processing; dsRNA-binding activity; DOUBLE-STRANDED-RNA; TLR3; DEFICIENCY; MEX-3; PROTEINS; LOCALIZATION; IMMUNITY; ENCEPHALITIS; RECOGNITION; ECTODOMAIN; COMPLEXES; INFECTION;

D O I：

10.1038/cr.2016.16

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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

引用

页码：288 / 303

页数：16

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