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"Activation of the interferon system
by short-interfering RNAs," by
Carol A. Sledz, Michelle Holko, Michael J. de Veer, Robert H. Silverman, and
Bryan R.G. Williams, Nature Cell Biology, 5(9): 834-9, September 2003.
[Authors' affiliations: Cleveland Clinic
Foundation, OH; Case Western Reserve University, Cleveland, OH]
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."
This 2003 report from Nature Cell Biology
was cited 47 times in current journal articles indexed by
Thomson Scientific during March-April 2005. Thanks to its latest two-month
tally, this is currently the second-most-cited paper in biology published in
the last two years, aside from reviews. Prior to the most recent bimonthly
count, citations to the paper have accrued as follows:
January-February 2005: 28 citations
November-December 2004: 20
September-October 2004: 25
July-August 2004: 19
May-June 2004: 11
March-April 2004: 26
January-February 2004: 8
November-December 2003: 3
September-October 2003: 3
Total citations to date: 190
SOURCE: Hot
Papers Database (Included with a subscription to the ISI print newsletter Science
Watch®, available from the ISI
Research Services Group. Packaged on a CD-ROM that is mailed with each Science
Watch issue, the Hot
Papers Database contains data on hundreds of highly cited papers published
during the last two years. User interface permits searching by author,
organization, journal, field, and more. Total citations, as well as citations
accrued during successive bimonthly periods, can be assessed and graphed. An
updated CD containing the most recent bimonthly data is mailed with every new
issue of Science
Watch,
six times a year. The CD also includes an electronic version of the Science
Watch
issue in HTML format, for personal desktop access.)
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