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

Lykke-Andersen, Karin and Gilchrist, Michael J. and Grabarek, Joanna B. and Das, Partha and Miska, Eric and Zernicka-Goetz, Magdalena (2008) Maternal Argonaute 2 Is Essential for Early Mouse Development at the Maternal-Zygotic Transition. Molecular Biology of the Cell, 19 (10). pp. 4383-4392. ISSN 1059-1524. PMCID PMC2555945. doi:10.1091/mbc.e08-02-0219.

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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.

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Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2008 by The American Society for Cell Biology. Authors grant to the general public, effective two months after publication of (i.e.,. the appearance of the edited manuscript in an online issue of MBoC), the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license ( Submitted February 28, 2008; Revised July 7, 2008; Accepted August 4, 2008. We thank David Glover and Jonathon Pines for helpful discussions and comments on the manuscript. This work was supported by a Wellcome Trust Senior Fellowship to M.Z.-G. K.L.-A. has been supported by the Wellcome Senior Fellowship to M.Z.-G. and by the Alfred Benzon Foundation and The Danish Natural Science Research Council (DNSRC), Denmark.
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Alfred Benzon FoundationUNSPECIFIED
Danish Natural Science Research CouncilUNSPECIFIED
Issue or Number:10
PubMed Central ID:PMC2555945
Record Number:CaltechAUTHORS:20190418-150055486
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Official Citation: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 Molecular Biology of the Cell 2008 19:10, 4383-4392
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94796
Deposited By: George Porter
Deposited On:23 Apr 2019 14:55
Last Modified:16 Nov 2021 17:07

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