Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys

Article Article scientifique Article Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys eng 2011 author Marq Jean-Baptiste 27225 author Hausmann Stéphane 29303 author Veillard Nicolas 682614 author Kolakofsky Daniel 25420 author Garcin Dominique 24296 6108-6116 10.1074/jbc.M110.186262 21159780 0021-9258 Arenavirus RNA genomes are initiated by a "prime and realign" mechanism, such that the initiating GTP is found as a single unpaired (overhanging) nucleotide when the complementary genome ends anneal to form double-stranded (ds) RNA panhandle structures. dsRNAs modeled on these structures do not induce interferon (IFN), as opposed to blunt-ended (5' ppp)dsRNA. This study examines whether these viral structures can also act as decoys, by trapping RIG-I in inactive dsRNA complexes. We examined the ability of various dsRNAs to activate the RIG-I ATPase (presumably a measure of helicase translocation on dsRNA) relative to their ability to induce IFN. We found that there is no simple relationship between these two properties, as if RIG-I can translocate on short dsRNAs without inducing IFN. Moreover, we found that (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide can in fact competitively inhibit the ability of blunt-ended (5' ppp)dsRNAs to induce IFN when co-transfected into cells and that this inhibition is strongly dependent on the presence of the 5' ppp. In contrast, (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide does not inhibit poly(I-C)-induced IFN activation, which is independent of the presence of a 5' ppp group. Arenavirus/genetics/metabolism Cell Line DEAD-box RNA Helicases/metabolism Enzyme Activation/drug effects/genetics Genome, Viral/physiology Humans Interferon Inducers/pharmacology Interferons/biosynthesis/genetics Poly I-C/pharmacology RNA, Double-Stranded/genetics/metabolism RNA, Viral/genetics/metabolism Dewey 616 54 Département de microbiologie et médecine moléculaire 21B false 216 Virologie moléculaire 275 The Journal of biological chemistry 286 8 7e82dd8a-f535-438f-8b1f-64ac237b07a6 Article (Published version) Restricted J. Biol. Chem.-2011-Marq-6108-16.pdf 1309502 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys	The Journal of biological chemistry			2011	650	0

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Veillard, Nicolas