Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Cells, Cultured; DEAD-box RNA Helicases; Humans; Interferon-alpha; Mice; Mice, Mutant Strains; Monocytes; Oligoribonucleotides; Polyphosphates; RNA Viruses; RNA, Double-Stranded; RNA, Viral
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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Citation: Immunity. 2009 Jul 17;31(1):25-34. Epub 2009 Jul 2. Link to article on publisher's site
Schlee, Martin; Roth, Andreas; Hornung, Veit; Hagmann, Christina Amparo; Wimmenauer, Vera; Barchet, Winfried; Coch, Christoph; Janke, Markus; Mihailovic, Aleksandra; Wardle, Greg; Juranek, Stefan; Kato, Hiroki; Kawai, Taro; Poeck, Hendrik; Fitzgerald, Katherine A.; Takeuchi, Osamu; Akira, Shizuo; Tuschl, Thomas; Latz, Eicke; Ludwig, Janos; and Hartmann, Gunther, "Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus" (2009). Infectious Diseases and Immunology Publications and Presentations. Paper 117.