Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus

Immunity. 2009 Jul 17;31(1):25-34. doi: 10.1016/j.immuni.2009.05.008.

Martin Schlee ¹, Andreas Roth, Veit Hornung, Cristina Amparo Hagmann, Vera Wimmenauer, Winfried Barchet, Christoph Coch, Markus Janke, Aleksandra Mihailovic, Greg Wardle, Stefan Juranek, Hiroki Kato, Taro Kawai, Hendrik Poeck, Katherine A Fitzgerald, Osamu Takeuchi, Shizuo Akira, Thomas Tuschl, Eicke Latz, Janos Ludwig, Gunther Hartmann

Affiliations

Affiliation

1 Institute of Clinical Chemistry and Pharmacology, University Hospital, University of Bonn, D-53127 Bonn, Germany.

PMID: 19576794 DOI: 10.1016/j.immuni.2009.05.008

Abstract

Antiviral immunity is triggered by immunorecognition of viral nucleic acids. The cytosolic helicase RIG-I is a key sensor of viral infections and is activated by RNA containing a triphosphate at the 5' end. The exact structure of RNA activating RIG-I remains controversial. Here, we established a chemical approach for 5' triphosphate oligoribonucleotide synthesis and found that synthetic single-stranded 5' triphosphate oligoribonucleotides were unable to bind and activate RIG-I. Conversely, the addition of the synthetic complementary strand resulted in optimal binding and activation of RIG-I. Short double-strand conformation with base pairing of the nucleoside carrying the 5' triphosphate was required. RIG-I activation was impaired by a 3' overhang at the 5' triphosphate end. These results define the structure of RNA for full RIG-I activation and explain how RIG-I detects negative-strand RNA viruses that lack long double-stranded RNA but do contain blunt short double-stranded 5' triphosphate RNA in the panhandle region of their single-stranded genome.

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