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Science 30 November 2007:
Vol. 318. no. 5855, pp. 1455 - 1458
DOI: 10.1126/science.1147347
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Reports

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}

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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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Vaccinia Virus Subverts a Mitochondrial Antiviral Signaling Protein-Dependent Innate Immune Response in Keratinocytes through Its Double-Stranded RNA Binding Protein, E3.
L. Deng, P. Dai, T. Parikh, H. Cao, V. Bhoj, Q. Sun, Z. Chen, T. Merghoub, A. Houghton, and S. Shuman (2008)
J. Virol. 82, 10735-10746
   Abstract »    Full Text »    PDF »
Structure and Function of LGP2, a DEX(D/H) Helicase That Regulates the Innate Immunity Response.
A. Murali, X. Li, C. T. Ranjith-Kumar, K. Bhardwaj, A. Holzenburg, P. Li, and C. C. Kao (2008)
J. Biol. Chem. 283, 15825-15833
   Abstract »    Full Text »    PDF »
Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner.
S. R. Nallagatla and P. C. Bevilacqua (2008)
RNA 14, 1201-1213
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)