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PMID:19576794

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Citation

Schlee, M, Roth, A, Hornung, V, Hagmann, CA, 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 and 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. Immunity 31:25-34

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.

Links

PubMed PMC2824854 Online version:10.1016/j.immuni.2009.05.008

Keywords

Animals; Cells, Cultured; DEAD-box RNA Helicases/genetics; DEAD-box RNA Helicases/immunology; Humans; Interferon-alpha/biosynthesis; Interferon-alpha/immunology; Mice; Mice, Mutant Strains; Monocytes/immunology; Monocytes/metabolism; Oligoribonucleotides/chemical synthesis; Oligoribonucleotides/immunology; Polyphosphates/immunology; Polyphosphates/metabolism; RNA Viruses/immunology; RNA, Double-Stranded/immunology; RNA, Double-Stranded/metabolism; RNA, Viral/immunology; RNA, Viral/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DDX58

enables

GO:0003725: double-stranded RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:DDX58

involved_in

GO:0032727: positive regulation of interferon-alpha production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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