Argonaute 2 is a key regulator for maternal mRNA degradation in mouse early embryos

Growing oocyte possesses high transcriptional activity, and accumulates massive maternal mRNAs and proteins, which control the initial stages of development. Maternal mRNA degradation (MRD) is required to remove repressive factors and enable zygotic genome activation (ZGA). To explore the function of Ago2 in MRD, we knocked Ago2 down by injection of small interfering RNA (siRNA) targeting Ago2 and AGO2 antibody into mouse zygote, and demonstrate that the deletion of Ago2 impairs normal early embryonic development, accompanied by abnormal MRD and ZGA. AGO2 guided by endosiRNAs could target maternal mRNAs and cooperate with P-bodies to promote MRD. We also indicate that AGO2 may associate with saRNA to regulate ZGA-dependent MRD. Our findings provide insights into the function of AGO2 on MRD and suggest its role in ZGA. Overall design: As the control, 2 replicates were performed at MII oocyte stage of wild type samples. The Ago2-kd embryo as well as control embryo at the 2- and 4-cell stage were collected and peformed for RNA-seq.