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Scientific article
English

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

Contributors

Marq, Jean-Baptiste; Kolakofsky, Daniel; Garcin, Dominique

Published in

The Journal of biological chemistry, vol. 285, no. 24, p. 18208-18216

Publication date

2010

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 Regions
  • Arenavirus/genetics
  • Cytoplasm/metabolism
  • Genome, Viral
  • Guanosine Triphosphate/chemistry
  • Humans
  • Interferons/metabolism
  • Models, Genetic
  • Nucleic Acid Conformation
  • Plasmids/metabolism
  • RNA, Double-Stranded/*genetics
  • RNA, Viral/*genetics
  • Receptors, Retinoic Acid/*metabolism
  • Ribonucleases/metabolism
  • Virus Replication

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

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: The Journal of biological chemistry, 2010, vol. 285, n° 24, p. 18208–18216. doi: 10.1074/jbc.M109.089425

Main files (1)

Article

Identifiers

Additional URL for this publication

http://www.jbc.org/content/285/24/18208.full.pdf

Journal ISSN

0021-9258
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Technical informations

Creation

23/05/2012 08:50:22

First validation

23/05/2012 08:50:22

Update

14/03/2023 17:34:20

Status update

14/03/2023 17:34:20

Last indexation

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