title: Absence of non-specific effects of RNA interference triggered by long double-stranded RNA in mouse oocytes.
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.
authors.affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104-6018, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Stein
authors.forename: Fanyi
authors.initials: F
authors.lastname: Zeng
authors.forename: Hua
authors.initials: H
authors.lastname: Pan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D007372:Interferons / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics*; D034741:RNA, Small Interfering
chemical_list: D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D012313:RNA; D007372:Interferons