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5'-Triphosphate RNA Is the Ligand for RIG-I

Science, 10 November 2006
Vol. 314, Issue 5801, p. 994-997
DOI: 10.1126/science.1132505

5'-Triphosphate RNA Is the Ligand for RIG-I

  1. Veit Hornung1,
  2. Jana Ellegast1,
  3. Sarah Kim1,
  4. Krzysztof Brzózka3,
  5. Andreas Jung2,
  6. Hiroki Kato2,
  7. Hendrik Poeck1,
  8. Shizuo Akira2,
  9. Karl-Klaus Conzelmann3,
  10. Martin Schlee4,
  11. Stefan Endres1,
  12. Gunther Hartmann4,*
  1. 1 Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.
  2. 2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita 565–0871, Osaka, Japan.
  3. 3 Department of Virology, Max von Pettenkofer Institute and Gene Center, University of Munich, 81377 Munich, Germany.
  4. 4 Division of Clinical Pharmacology, University Hospital, University of Bonn, 53105 Bonn, Germany.
  1. * To whom correspondence should be addressed. E-mail: gunther.hartmann{at}ukb.uni-bonn.de

Abstract

The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5′-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid–inducible protein I (RIG-I)–mediated detection of RNA molecules. Detection of 5′-triphosphate RNA is abrogated by capping of the 5′-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-α response in a phosphatase-sensitive manner. 5′-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5′-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.

  • Received for publication 14 July 2006.
  • Accepted for publication 18 September 2006.

Citation:

V. Hornung, J. Ellegast, S. Kim, K. Brzózka, A. Jung, H. Kato, H. Poeck, S. Akira, K.-K. Conzelmann, M. Schlee, S. Endres, and G. Hartmann, 5'-Triphosphate RNA Is the Ligand for RIG-I. Science 314, 994-997 (2006).

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Sensing of RNA Viruses: a Review of Innate Immune Receptors Involved in Recognizing RNA Virus Invasion
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Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity
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Two MicroRNAs Encoded within the Bovine Herpesvirus 1 Latency-Related Gene Promote Cell Survival by Interacting with RIG-I and Stimulating NF-{kappa}B-Dependent Transcription and Beta Interferon Signaling Pathways
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