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RIG-I self-oligomerization is either dispensable or very transient for signal transduction.

Abstract
Effective host defence against viruses depends on the rapid triggering of innate immunity through the induction of a type I interferon (IFN) response. To this end, microbe-associated molecular patterns are detected by dedicated receptors. Among them, the RIG-I-like receptors RIG-I and MDA5 activate IFN gene expression upon sensing viral RNA in the cytoplasm. While MDA5 forms long filaments in vitro upon activation, RIG-I is believed to oligomerize after RNA binding in order to transduce a signal. Here, we show that in vitro binding of synthetic RNA mimicking that of Mononegavirales (Ebola, rabies and measles viruses) leader sequences to purified RIG-I does not induce RIG-I oligomerization. Furthermore, in cells devoid of endogenous functional RIG-I-like receptors, after activation of exogenous Flag-RIG-I by a 62-mer-5'ppp-dsRNA or by polyinosinic:polycytidylic acid, a dsRNA analogue, or by measles virus infection, anti-Flag immunoprecipitation and specific elution with Flag peptide indicated a monomeric form of RIG-I. Accordingly, when using the Gaussia Luciferase-Based Protein Complementation Assay (PCA), a more sensitive in cellula assay, no RIG-I oligomerization could be detected upon RNA stimulation. Altogether our data indicate that the need for self-oligomerization of RIG-I for signal transduction is either dispensable or very transient.
AuthorsJade Louber, Eva Kowalinski, Louis-Marie Bloyet, Joanna Brunel, Stephen Cusack, Denis Gerlier
JournalPloS one (PLoS One) Vol. 9 Issue 9 Pg. e108770 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID25259935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Viral
  • Receptors, Immunologic
  • Interferon-beta
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
Topics
  • Animals
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases (metabolism)
  • HEK293 Cells
  • Humans
  • Immunity, Innate (physiology)
  • Interferon-beta (genetics)
  • Promoter Regions, Genetic
  • RNA, Viral (genetics)
  • Receptors, Immunologic
  • Signal Transduction (physiology)
  • Vero Cells

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