Genomewide view of gene silencing by small interfering RNAs

Journal Article

RNA interference (RNAi) is an evolutionarily conserved mechanism in plant and animal cells that directs the degradation of messenger RNAs homologous to short double-stranded RNAs termed small interfering RNA (siRNA). The ability of siRNA to direct gene silencing in mammalian cells has raised the possibility that siRNA might be used to investigate gene function in a high throughput fashion or to modulate gene expression in human diseases. The specificity of siRNA-mediated silencing, a critical consideration in these applications, has not been addressed on a genomewide scale. Here we show that siRNA-induced gene silencing of transient or stably expressed mRNA is highly gene-specific and does not produce secondary effects detectable by genomewide expression profiling. A test for transitive RNAi, extension of the RNAi effect to sequences 5′ of the target region that has been observed in Caenorhabditis elegans, was unable to detect this phenomenon in human cells.

Full Text

Duke Authors

Cited Authors

  • Chi, J-T; Chang, HY; Wang, NN; Chang, DS; Dunphy, N; Brown, PO

Published Date

  • 2003

Published In

  • Proceedings of the National Academy of Sciences of the United States of America

Volume / Issue

  • 100 / 11

Start / End Page

  • 6343 - 6346

PubMed ID

  • 12730368

Digital Object Identifier (DOI)

  • 10.1073/pnas.1037853100