Maternal Argonaute 2 Is Essential for Early Mouse Development at the Maternal-Zygotic Transition
- 1 October 2008
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 19 (10), 4383-4392
- https://doi.org/10.1091/mbc.e08-02-0219
Abstract
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.Keywords
This publication has 73 references indexed in Scilit:
- Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytesNature, 2008
- A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathwayGenes & Development, 2007
- Distance constraints between microRNA target sites dictate efficacy and cooperativityNucleic Acids Research, 2007
- AU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2Cell, 2007
- Illuminating the silence: understanding the structure and function of small RNAsNature Reviews Molecular Cell Biology, 2007
- Small dsRNAs induce transcriptional activation in human cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- Combinatorial microRNA target predictionsNature Genetics, 2005
- Mechanisms of gene silencing by double-stranded RNANature, 2004
- MicroRNAs: small RNAs with a big role in gene regulationNature Reviews Genetics, 2004
- RNA interferenceNature, 2002