Activation of the interferon system by short-interfering RNAs View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-09

AUTHORS

Carol A. Sledz, Michelle Holko, Michael J. de Veer, Robert H. Silverman, Bryan R.G. Williams

ABSTRACT

RNA interference (RNAi) is a powerful tool used to manipulate gene expression or determine gene function. One technique of expressing the short double-stranded (ds) RNA intermediates required for interference in mammalian systems is the introduction of short-interfering (si) RNAs. Although RNAi strategies are reliant on a high degree of specificity, little attention has been given to the potential non-specific effects that might be induced. Here, we found that transfection of siRNAs results in interferon (IFN)-mediated activation of the Jak-Stat pathway and global upregulation of IFN-stimulated genes. This effect is mediated by the dsRNA-dependent protein kinase, PKR, which is activated by 21-base-pair (bp) siRNAs and required for upregulation of IFN-beta in response to siRNAs. In addition, we show by using cell lines deficient in specific components mediating IFN action that the RNAi mechanism itself is independent of the interferon system. Thus, siRNAs have broad and complicating effects beyond the selective silencing of target genes when introduced into cells. This is of critical importance, as siRNAs are currently being explored for their potential therapeutic use. More... »

PAGES

834

Journal

TITLE

Nature Cell Biology

ISSUE

9

VOLUME

5

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncb1038

    DOI

    http://dx.doi.org/10.1038/ncb1038

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1020695123

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12942087


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    RDF/XML is a standard XML format for linked data.

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