Maternal Argonaute 2 is essential for early mouse development at the maternal-zygotic transition.
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.
Lykke-Andersen
Karin
K
Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, CB2 1NR, United Kingdom.
Gilchrist
Michael J
MJ
Grabarek
Joanna B
JB
Das
Partha
P
Miska
Eric
E
Zernicka-Goetz
Magdalena
M
D000818:Animals; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009693:Nucleic Acid Hybridization; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D023121:RNA, Messenger, Stored / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics; D015053:Zygote / Q000378:metabolism*
C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D012330:RNA, Double-Stranded; D023121:RNA, Messenger, Stored; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D049452:Green Fluorescent Proteins