The cricket paralysis virus suppressor inhibits microRNA silencing mediated by the Drosophila Argonaute-2 protein

PLoS One. 2015 Mar 20;10(3):e0120205. doi: 10.1371/journal.pone.0120205. eCollection 2015.

Abstract

Small RNAs are potent regulators of gene expression. They also act in defense pathways against invading nucleic acids such as transposable elements or viruses. To counteract these defenses, viruses have evolved viral suppressors of RNA silencing (VSRs). Plant viruses encoded VSRs interfere with siRNAs or miRNAs by targeting common mediators of these two pathways. In contrast, VSRs identified in insect viruses to date only interfere with the siRNA pathway whose effector Argonaute protein is Argonaute-2 (Ago-2). Although a majority of Drosophila miRNAs exerts their silencing activity through their loading into the Argonaute-1 protein, recent studies highlighted that a fraction of miRNAs can be loaded into Ago-2, thus acting as siRNAs. In light of these recent findings, we re-examined the role of insect VSRs on Ago-2-mediated miRNA silencing in Drosophila melanogaster. Using specific reporter systems in cultured Schneider-2 cells and transgenic flies, we showed here that the Cricket Paralysis virus VSR CrPV1-A but not the Flock House virus B2 VSR abolishes silencing by miRNAs loaded into the Ago-2 protein. Thus, our results provide the first evidence that insect VSR have the potential to directly interfere with the miRNA silencing pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism*
  • Dicistroviridae / classification
  • Dicistroviridae / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / virology*
  • Insect Viruses / metabolism*
  • MicroRNAs / metabolism
  • RNA Interference*
  • Viral Proteins / metabolism*

Substances

  • AGO2 protein, Drosophila
  • Argonaute Proteins
  • Drosophila Proteins
  • MicroRNAs
  • Viral Proteins

Grants and funding

Centre National de la Recherché Scientifique University Pierre et Marie Curie Institut National de la Santé et de la Recherche Médicale Agence Nationale de la Recherche [grant number ANR BLAN 1210 01 “nuclear endosiRNA”] to CA and Fondation pour la Recherche Médicale [post-doctoral fellowship] to SD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.