Miyashita M, Oshiumi H, Matsumoto M, Seya T

The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DExD/H box RNA helicase similar to S. cerevisiae Ski2, a cofactor of RNA exosome, a protein complex required for the integrity of cytoplasmic RNA. The ...

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expression of DDX60 increases after viral infection, and the protein localizes at cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein. The protein also binds to MDA5 and LGP2, but not to downstream factors, IPS-1 and IKK-ε. Knockdown analyses shows that DDX60 is required for RIG-I or MDA5-dependent type I interferon and interferon-inducible gene expressions in response to viral infection. However, DDX60 is dispensable for TLR3-mediated signaling. Purified DDX60 helicase domain possesses the activity to bind to viral RNA and DNA. Expression of DDX60 promotes the binding of RIG-I to double-strand RNA. Taken together, our analyses indicate that DDX60 is a novel antiviral helicase promoting RIG-I-like receptor mediated signaling.

Date: Jul. 25, 2011

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