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Vol. 19, Issue 10, 4383-4392, October 2008

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Maternal Argonaute 2 Is Essential for Early Mouse Development at the Maternal-Zygotic Transition

Karin Lykke-Andersen^*, Michael J. Gilchrist, Joanna B. Grabarek, Partha Das, Eric Miska, and Magdalena Zernicka-Goetz

Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, CB2 1NR, United Kingdom

Submitted February 28, 2008; Revised July 7, 2008; Accepted August 4, 2008
Monitoring Editor: Marianne Bronner-Fraser

Activation of zygotic gene expression in the two-cell mouse embryo is associated with destruction of maternally inherited transcripts, an important process for embryogenesis about which little is understood. We asked whether the Argonaute (Ago)/RNA-induced silencing complex, providing the mRNA "slicer" activity in gene silencing, might contribute to this process. Here we show that Ago2, 3, and 4 transcripts are contributed to the embryo maternally. By systematic knockdown of maternal Ago2, 3, and 4, individually and in combination, we find that only Ago2 is required for development beyond the two-cell stage. Knockdown of Ago2 stabilizes one set of maternal mRNAs and reduces zygotic transcripts of another set of genes. Ago2 is localized in mRNA-degradation P-bodies analogous to those that function in RNAi-like mechanisms in other systems. Profiling the expression of microRNAs throughout preimplantation development identified several candidates that could potentially work with Ago2 to mediate degradation of specific mRNAs. However, their low abundance raises the possibility that other endogenous siRNAs may also participate. Together, our results demonstrate that maternal expression of Ago2 is essential for the earliest stages of mouse embryogenesis and are compatible with the notion that degradation of a proportion of maternal messages involves the RNAi-machinery.

Author contributions: K.L.A. and M.Z.G. drafted the manuscript; K.L.A. prepared data for Figures 1, 2, 3, 4, Supplementary Figures S1, S2, and S3, and Supplementary Table S1. Data for Supplementary Tables S2, S3, and S4 were prepared by M.G., J.B.G., P.D., and E.M.

Present addresses: * Institute of Medical Biochemistry, University of Aarhus, Ole Worms Alle 1170, DK-8000 Aarhus C, Denmark;

Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, United Kingdom.

Address correspondence to: Magdalena Zernicka-Goetz (mzg{at}mole.bio.cam.ac.uk)

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