A model for the role of ADAR1 in innate immunity.

<p>(A) DsRNA that is generated during transcription is edited by ADARs. The dsRNA contain inosine that can bind to the RLRs, MDA5 and RIG-I, in the cytoplasm and inhibit their activation. (B) During a viral infection, or if ADAR1 is inactive, unedited dsRNA is present in the cytoplasm. This dsRNA binds to MDA5 and RIG-I, activating MAVS which, in turn, leads to the phosphorylation of IRF3 and its translocation into the nucleus and induces the type 1 interferon response. (C) The ADAR1 isoform p150 is induced by interferon late in the response. This isoform is predominantly cytoplasmic and it edits all dsRNA either of viral or cellular origin. This generates inosine containing dsRNA that can inhibit the RLR receptors, thus turning off the interferon response as the transcription factor IRF9 is unable to continue to transcribe the ISGs.