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Expression profiling reveals off-target gene regulation by RNAi

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Abstract

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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Figure 1: Expression profiling reveals siRNA sequence-specific and concentration-dependent gene expression patterns.
Figure 2: Kinetic and sequence analysis of MAPK14 knockdown by RNAi.

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  • 30 May 2003

    replaced PDF with correct version (print was correct), ammended PDF with errata, footnote in SGML at Figure 1 callouts and legend

Notes

  1. *Note: In the version of this article initially published online, the arrow labeled Mapk14 panel C was placed over the wrong bar. It should have pointed to the most prominent bar in all concentrations. This has been corrected in the online and print versions of the article.

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Acknowledgements

We thank G. Schimmack, S. Kim, M. Imakura and J. McLarnan for expert technical assistance, M. Biery for assistance with computer graphics and the Rosetta Gene Expression Laboratory for microarray work.

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Correspondence to Aimee L Jackson or Steven R Bartz.

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The authors declare no competing financial interests.

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Jackson, A., Bartz, S., Schelter, J. et al. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21, 635–637 (2003). https://doi.org/10.1038/nbt831

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