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Unpaired 5' ppp-nucleotides, as found in arenavirus double-stranded RNA panhandles, are not recognized by RIG-I

Published in Journal of Biological Chemistry. 2010, vol. 285, no. 24, p. 18208-18216
Abstract Arenavirus and bunyavirus RNA genomes are unusual in that they are found in circular nucleocapsids, presumably due to the annealing of their complementary terminal sequences. Moreover, arenavirus genome synthesis initiates with GTP at position +2 of the template rather than at the precise 3' end (position +1). After formation of a dinucleotide, 5' pppGpC(OH) is then realigned on the template before this primer is extended. The net result of this "prime and realign" mechanism of genome initiation is that 5' pppG is found as an unpaired 5' nucleotide when the complementary genome ends anneal to form a double-stranded (dsRNA) panhandle. Using 5' pppRNA made in vitro and purified so that all dsRNA side products are absent, we have determined that both this 5' nucleotide overhang, as well as mismatches within the dsRNA (as found in some arenavirus genomes), clearly reduce the ability of these model dsRNAs to induce interferon upon transfection into cells. The presence of this unpaired 5' ppp-nucleotide is thus another way that some viruses appear to use to avoid detection by cytoplasmic pattern recognition receptors.
Keywords 5' Untranslated RegionsArenavirus/geneticsCytoplasm/metabolismGenome, ViralGuanosine Triphosphate/chemistryHumansInterferons/metabolismModels, GeneticNucleic Acid ConformationPlasmids/metabolismRNA, Double-Stranded/*geneticsRNA, Viral/*geneticsReceptors, Retinoic Acid/*metabolismRibonucleases/metabolismVirus Replication
PMID: 20400512
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Other version: http://www.jbc.org/content/285/24/18208.full.pdf
Research group Virologie moléculaire (275)
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MARQ, Jean-Baptiste, KOLAKOFSKY, Daniel, GARCIN, Dominique. Unpaired 5' ppp-nucleotides, as found in arenavirus double-stranded RNA panhandles, are not recognized by RIG-I. In: Journal of Biological Chemistry, 2010, vol. 285, n° 24, p. 18208-18216. doi: 10.1074/jbc.M109.089425 https://archive-ouverte.unige.ch/unige:21113

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Deposited on : 2012-05-23

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