Expression of LINE-1 retroposons is essential for murine preimplantation development.
In higher eukaryotes, reverse transcriptase (RT) activities are encoded by a variety of endogenous retroviruses and retrotransposable elements. We previously found that mouse preimplantation embryos are endowed with an endogenous RT activity. Inhibition of that activity by the non nucleosidic inhibitor nevirapine or by microinjection of anti-RT antibody caused early embryonic developmental arrest. Those experiments indicated that RT is required for early development, but did not identify the responsible coding elements. We now show that microinjection of morpholino-modified antisense oligonucleotides targeting the 5' end region of active LINE-1 retrotransposons in murine zygotes irreversibly arrests preimplantation development at the two- and four-cell stages; the overall level of functional RT is concomitantly downregulated in arrested embryos. Furthermore, we show that the induction of embryo developmental arrest is associated with a substantial reprogramming of gene expression. Together, these results support the conclusion that expression of LINE-1 retrotransposons is required for early embryo preimplantation development.
Beraldi
Rosanna
R
University of Siena, Siena, Italy.
Pittoggi
Carmine
C
Sciamanna
Ilaria
I
Mattei
Elisabetta
E
Spadafora
Corrado
C
D000818:Animals; D000831:Animals, Newborn; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D012313:RNA / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics
D016376:Oligonucleotides, Antisense; D012313:RNA