Inactivation of the type I interferon pathway reveals long double‐stranded RNA‐mediated RNA interference in mammalian cells

• Pierre V Maillard ^[1] ; Annemarthe G Van der Veen ^[1] ; Safia Deddouche‐Grass ^[1] ; Neil C Rogers ^[1] ; Andres Merits ^[2] ; Caetano Reis e Sousa ^[1]
  1. [1] Francis Crick Institute

     Francis Crick Institute

     Reino Unido

     
  2. [2] 2 Institute of Technology University of Tartu Tartu Estonia
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 35, Nº. 23, 2016, págs. 2505-2518
• Idioma: inglés
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• Resumen

  • RNA interference (RNAi) elicited by long double‐stranded (ds) or base‐paired viral RNA constitutes the major mechanism of antiviral defence in plants and invertebrates. In contrast, it is controversial whether it acts in chordates. Rather, in vertebrates, viral RNAs induce a distinct defence system known as the interferon (IFN) response. Here, we tested the possibility that the IFN response masks or inhibits antiviral RNAi in mammalian cells. Consistent with that notion, we find that sequence‐specific gene silencing can be triggered by long dsRNAs in differentiated mouse cells rendered deficient in components of the IFN pathway. This unveiled response is dependent on the canonical RNAi machinery and is lost upon treatment of IFN‐responsive cells with type I IFN. Notably, transfection with long dsRNA specifically vaccinates IFN‐deficient cells against infection with viruses bearing a homologous sequence. Thus, our data reveal that RNAi constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.