title: RNAi and expression of retrotransposons MuERV-L and IAP in preimplantation mouse embryos.
abstract: Both murine endogenous retrovirus-L (MuERV-L) and intracisternal A particle (IAP), two autonomous long terminal repeat (LTR) retrotransposons, are activated during genome activation in the preimplantation mouse embryo, and both sense and antisense transcripts are detected in 2-cell and 8-cell stage embryos. Because RNA interference (RNAi) functions in the preimplantation mouse embryo, we analyzed the relationship between RNAi and MuERV-L and IAP expression by inhibiting RNAi and measuring relative changes of the levels of these transcripts. We inhibited the initial step in the RNAi pathway by injecting 1-cell embryos with mDicer siRNA or long mDicer dsRNA and analyzed MuERV-L and IAP expression at the 8-cell stage. This approach resulted in the targeted destruction of mDicer mRNA, but not Hdac1 mRNA, inhibited the RNAi pathway, and resulted in a 50% increase in IAP and MuERV-L transcript abundance. These results suggest that RNAi constrains expression of repetitive parasitic sequences in preimplantation embryos, and thereby contributes to preserving genomic integrity at a stage of development when the organism consists of only a few cells.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA.
authors.forename: Petr
authors.initials: P
authors.lastname: Svoboda
authors.forename: Paula
authors.initials: P
authors.lastname: Stein
authors.forename: Martin
authors.initials: M
authors.lastname: Anger
authors.forename: Emily
authors.initials: E
authors.lastname: Bernstein
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism*; D007426:Genes, Intracisternal A-Particle / Q000187:drug effects; D051379:Mice; D008845:Microinjections; D034622:RNA Interference / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000008:administration & dosage / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology; D018626:Retroelements / Q000187:drug effects
chemical_list: D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D018626:Retroelements