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5'-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops
Subba Rao Nallagatla,1*
Jungwook Hwang,2*
Rebecca Toroney,1
Xiaofeng Zheng,1,3
Craig E. Cameron,2,4
Philip C. Bevilacqua1
Abstract:
Molecular patterns in pathogenic RNAs can be recognized by theinnate immune system, and a component of this response is theinterferon-induced enzyme RNA-activated protein kinase (PKR).The major activators of PKR have been proposed to be long double-strandedRNAs. We report that RNAs with very limited secondary structuresactivate PKR in a 5'-triphosphate–dependent fashion invitro and in vivo. Activation of PKR by 5'-triphosphate RNAis independent of RIG-I and is enhanced by treatment with type1 interferon (IFN-). Surveillance of molecular features at the5' end of transcripts by PKR presents a means of allowing pathogenicRNA to be distinguished from self-RNA. The evidence presentedhere suggests that this form of RNA-based discrimination maybe a critical step in mounting an early immune response.
1 Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA. 2 Integrative Biosciences, Pennsylvania State University, University Park, PA 16802, USA. 3 Department of Biochemistry and Molecular Biology, Life Sciences College, Peking University, Beijing 100871, China. 4 Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: pcb{at}chem.psu.edu (P.C.B.); cec9{at}psu.edu (C.E.C.)
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[DOI: 10.1126/stke.4152007tw442] |Abstract »
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). 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. 
To whom correspondence should be addressed. E-mail: 
