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
Immunology and Infectious Disease
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.
DOI of Published Version
Immunity. 2009 Jul 17;31(1):25-34. Epub 2009 Jul 2. Link to article on publisher's site
Schlee M, Roth A, Hornung V, Hagmann C, Wimmenauer V, Barchet W, Coch C, Janke M, Mihailovic A, Wardle G, Juranek S, Kato H, Kawai T, Poeck H, Fitzgerald KA, Takeuchi O, Akira S, Tuschl T, Latz E, Ludwig J, Hartmann G. (2009). Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Infectious Diseases and Immunology Publications. https://doi.org/10.1016/j.immuni.2009.05.008. Retrieved from https://escholarship.umassmed.edu/infdis_pp/117