Intracellular RNA recognition and signaling. Cytosolic dsRNA or 5′-triphosphate ssRNA is recognized primarily by the cytoplasmic RNA helicases RIG-I and MDA5, which mediate interaction with the adaptor IPS-1, localized to mitochondria, and trigger signaling to NF-κB and IRF3 via IKK and TBK/IKKɛ, respectively. dsRNA can also be recognized by TLR3 localized in the endosomal compartment or by cytosolic PKR, but whereas TLR3 triggers signaling to NF-κB and IRF3, PKR instead activates NF-κB and MAPKs. Finally, ssRNA is recognized by TLR7/8 in endosomes and induces signaling to IRF7 as well as to NF-κB and MAPKs (not shown in the figure).