ADAR1: “Editor-in-Chief” of Cytoplasmic Innate Immunity

Figures

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  Figure 1. The domain architecture of ADAR1 isoforms p150 and p110. NES, nuclear export signal; dsRBD, double-stranded RNA binding domain; NLS, nuclear localization signal.

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  Figure 2. ADAR1's dampening effect on immune activity prevents autoimmunity in steady-state, but should be regulated during viral infection.

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  Figure 3. ADAR1 balances self-tolerance and immune activity by modulating canonical antiviral pathways induced by dsRNA. (A) Adenosine to inosine editing or binding of the cytoplasmic ADAR1 isoform p150 or the nuclear p110 to extended dsRNA duplexes prevents their detection by cytoplasmic antiviral signaling pathways, including RIG-I like receptor-, OAS/RNAseL-, and PKR pathways. These dsRNA duplexes can be of viral origin, but in the absence of ADAR1 (B) endogenous dsRNAs—which are likely to originate from inverted Alu repeats or other sources (e.g., mitochondrial dsRNAs)—can also serve as a substrate for antiviral signaling, leading to immune activation, and possibly autoimmunity. Blocking the activation of these pathways prevents IFN-I production, translation arrest, and apoptosis, but this must be tightly regulated in order to not create an environment that favors virus replication.