5'-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops
Nallagatla, Subba Rao | Hwang, Jungwook | Toroney, Rebecca | Zheng, Xiaofeng | Cameron, Craig E. | Bevilacqua, Philip C.
Molecular patterns in pathogenic RNAs can be recognized by the innate immune system, and a component of this response is the interferon-induced enzyme RNA-activated protein kinase (PKR). The major activators of PKR have been proposed to be long double-stranded RNAs. We report that RNAs with very limited secondary structures activate PKR in a 5'-triphosphate-dependent fashion in vitro and in vivo. Activation of PKR by 5'-triphosphate RNA is independent of RIG-I and is enhanced by treatment with type 1 interferon (IFN-α). Surveillance of molecular features at the 5' end of transcripts by PKR presents a means of allowing pathogenic RNA to be distinguished from self-RNA. The evidence presented here suggests that this form of RNA-based discrimination may be a critical step in mounting an early immune response.Show more [+] Less [-]