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Inactivation of the type I interferon pathway reveals long double‐stranded RNA ‐mediated RNA interference in mammalian cells
Author(s) -
Maillard Pierre V,
Van der Veen Annemarthe G,
DeddoucheGrass Safia,
Rogers Neil C,
Merits Andres,
Reis e Sousa Caetano
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695086
Subject(s) - rna , rna silencing , biology , interferon , rna interference , microbiology and biotechnology , rna induced silencing complex , gene , interferon type i , small interfering rna , virology , genetics
RNA interference ( RNA i) 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 RNA s induce a distinct defence system known as the interferon ( IFN ) response. Here, we tested the possibility that the IFN response masks or inhibits antiviral RNA i in mammalian cells. Consistent with that notion, we find that sequence‐specific gene silencing can be triggered by long ds RNA s in differentiated mouse cells rendered deficient in components of the IFN pathway. This unveiled response is dependent on the canonical RNA i machinery and is lost upon treatment of IFN ‐responsive cells with type I IFN . Notably, transfection with long ds RNA specifically vaccinates IFN ‐deficient cells against infection with viruses bearing a homologous sequence. Thus, our data reveal that RNA i constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.