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.
Original language | English (US) |
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Pages (from-to) | 288-303 |
Number of pages | 16 |
Journal | Cell research |
Volume | 26 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2016 |
Externally published | Yes |
Keywords
- dsRNA-binding activity
- Mex3B
- proteolytic processing
- TLR3
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology