1. Absence of non-specific effects of RNA interference triggered by long double-stranded RNA in mouse oocytes
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Stein, Paula, Zeng, Fanyi, Pan, Hua, and Schultz, Richard M.
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Messenger RNA -- Analysis ,Biological response modifiers -- Analysis ,Protein biosynthesis -- Analysis ,Gene expression -- Analysis ,Cell research -- Analysis ,Biological sciences - Abstract
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.08.015 Byline: Paula Stein, Fanyi Zeng, Hua Pan, Richard M. Schultz Keywords: RNAi; dsRNA; Oocyte; Interferon response; Off-targeting Abstract: RNA interference (RNAi) is a conserved eukaryotic mechanism by which double-stranded RNA (dsRNA) triggers the sequence-specific degradation of homologous mRNAs. Recent concerns have arisen in mammalian systems about off-target effects of RNAi, as well as an interferon response. Most mammalian cells respond to long dsRNAs by inducing an antiviral response mediated by interferon that leads to general inhibition of protein synthesis and nonspecific degradation of mRNAs. Moreover, recent reports demonstrate that under certain conditions, short interfering RNAs (siRNAs, 21-25 bp) may activate the interferon system. Mouse oocytes and preimplantation embryos apparently lack this response, as potent and specific inhibition of gene expression triggered by long dsRNA is observed in these cells. In the present study, we analyzed the global pattern of gene expression by microarray analysis in transgenic mouse oocytes expressing long dsRNA and find no evidence of off-targeting. We also report that genes involved in the interferon response pathway are not expressed in mouse oocytes, even after exposure for an extended period of time to long dsRNA. Author Affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104-6018, USA Article History: Received 12 July 2005; Revised 11 August 2005; Accepted 12 August 2005
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- 2005