Journal
CELL RESEARCH
Volume 26, Issue 3, Pages 288-303Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2016.16
Keywords
TLR3; Mex3B; proteolytic processing; dsRNA-binding activity
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Funding
- National Science Fund for Distinguished Young Scholars [31425010]
- National Natural Science Foundation of China [31321001, 31270932, 31400743]
- Ministry of Science and Technology of China [2014CB542603, 2015CB554302]
- 10000 Talent Program
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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.
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