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Science 318 (5855): 1455-1458

Copyright © 2007 by the American Association for the Advancement of Science

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{dagger} Philip C. Bevilacqua1{dagger}

Abstract: 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-{alpha}). 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.

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.

{dagger} 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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