RNA interference is thought to require near-identity between the
small interfering RNA (siRNA) and its cognate mRNA. Here, we used gene
expression profiling to characterize the specificity of gene silencing by
siRNAs in cultured human cells. Transcript profiles revealed siRNA-specific
rather than target-specific signatures, including direct silencing of
nontargeted genes containing as few as eleven contiguous nucleotides of
identity to the siRNA. These results demonstrate that siRNAs may cross-react
with targets of limited sequence similarity.
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