Activation of PKR by complex RNAs. (a) HIV TAR RNA undergoes dimerization, which effectively doubles its length from 23 to 46 bp. The 23 bp TAR monomer inhibits PKR, whereas the 46 bp dimer activates PKR. The former binds PKR as a monomer, whereas the latter binds it as a dimer. (b) HCV IRES containing four domains, with domain II highlighted. Domain II contains base paired and loop segments, both of which contribute to activation and provide the equivalent of ~33 bp of dsRNA. This element has been shown to mimic A-form dsRNA, including the loop interactions boxed in green [36]. (c) Pseudoknot from the IFN-γ mRNA. The 124 nt 5’-untranslated region is blue, and the coding sequence is red. This domain forms an extended structure with several base pairing elements that also leads to the equivalent of ~33 bp of dsRNA [50]. In both panels, a dimer of PKR appears to assemble onto the ~33 bp region, leading to an activated state. Panel (b) is adapted with permission from [63].