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Title

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

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Published in Journal of Biological Chemistry. 2011, vol. 286, no. 8, p. 6108-16
Abstract 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.
Keywords Arenavirus/genetics/metabolismCell LineDEAD-box RNA Helicases/metabolismEnzyme Activation/drug effects/geneticsGenome, Viral/physiologyHumansInterferon Inducers/pharmacologyInterferons/biosynthesis/geneticsPoly I-C/pharmacologyRNA, Double-Stranded/genetics/metabolismRNA, Viral/genetics/metabolism
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PMID: 21159780
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Article (Published version) (1.2 MB) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Virologie moléculaire (275)
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MARQ, Jean-Baptiste et al. Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys. In: Journal of Biological Chemistry, 2011, vol. 286, n° 8, p. 6108-16. https://archive-ouverte.unige.ch/unige:38153

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Deposited on : 2014-06-25

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