Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 30 November 2007:
Vol. 318. no. 5855, pp. 1455 - 1458
DOI: 10.1126/science.1147347
Prev | Table of Contents | Next

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.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Sequence-non-specific effects of RNA interference triggers and microRNA regulators.
M. Olejniczak, P. Galka, and W. J. Krzyzosiak (2009)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation.
R. Kenworthy, D. Lambert, F. Yang, N. Wang, Z. Chen, H. Zhu, F. Zhu, C. Liu, K. Li, and H. Tang (2009)
Nucleic Acids Res. 37, 6587-6599
   Abstract »    Full Text »    PDF »
The ssRNA Genome of Human Rhinovirus Induces a Type I IFN Response but Fails to Induce Maturation in Human Monocyte-Derived Dendritic Cells.
C. Schrauf, S. Kirchberger, O. Majdic, M. Seyerl, G.-J. Zlabinger, K. M. Stuhlmeier, M. Sachet, J. Seipelt, and J. Stockl (2009)
J. Immunol. 183, 4440-4448
   Abstract »    Full Text »    PDF »
Baculovirus Induces Type I Interferon Production through Toll-Like Receptor-Dependent and -Independent Pathways in a Cell-Type-Specific Manner.
T. Abe, Y. Kaname, X. Wen, H. Tani, K. Moriishi, S. Uematsu, O. Takeuchi, K. J. Ishii, T. Kawai, S. Akira, et al. (2009)
J. Virol. 83, 7629-7640
   Abstract »    Full Text »    PDF »
NSs Protein of Rift Valley Fever Virus Induces the Specific Degradation of the Double-Stranded RNA-Dependent Protein Kinase.
M. Habjan, A. Pichlmair, R. M. Elliott, A. K. Overby, T. Glatter, M. Gstaiger, G. Superti-Furga, H. Unger, and F. Weber (2009)
J. Virol. 83, 4365-4375
   Abstract »    Full Text »    PDF »
Human Respiratory Syncytial Virus Nonstructural Protein NS2 Antagonizes the Activation of Beta Interferon Transcription by Interacting with RIG-I.
Z. Ling, K. C. Tran, and M. N. Teng (2009)
J. Virol. 83, 3734-3742
   Abstract »    Full Text »    PDF »
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses.
T. H. Mogensen (2009)
Clin. Microbiol. Rev. 22, 240-273
   Abstract »    Full Text »    PDF »
Severe Acute Respiratory Syndrome Coronavirus Triggers Apoptosis via Protein Kinase R but Is Resistant to Its Antiviral Activity.
V. Krahling, D. A. Stein, M. Spiegel, F. Weber, and E. Muhlberger (2009)
J. Virol. 83, 2298-2309
   Abstract »    Full Text »    PDF »
The RNA-activated Protein Kinase Enhances the Induction of Interferon-{beta} and Apoptosis Mediated by Cytoplasmic RNA Sensors.
C. S. McAllister and C. E. Samuel (2009)
J. Biol. Chem. 284, 1644-1651
   Abstract »    Full Text »    PDF »
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 »


To Advertise     Find Products

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