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

Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus.
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DOI:
10.1016/j.immuni.2009.05.008
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发表时间:
2009-07-17
期刊:
影响因子:
32.4
通讯作者:
Hartmann, Gunther
Hartmann, Gunther
中科院分区:
医学1区
文献类型:
--
作者:
Schlee, Martin;Roth, Andreas;Hornung, Veit;Hagmann, Cristina 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;Hartmann, Gunther

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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 which lack long double-stranded RNA but do contain panhandle blunt short double-stranded 5′triphosphate RNA in their single-stranded genome.
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