Abundant non-A residues in the poly(A) tail orchestrate the mouse oocyte-to-embryo transition

Non-A (U, G, and C) residues can be added to the 5-end, internal, and 3-end positions of poly(A) tails of RNA transcripts, and some of these have been shown to regulate mRNA stability. The mammalian oocyte-to-embryo transition (OET) relies on post-transcriptional regulation of maternal RNA, because transcription is silent during this process until the point of zygotic genome activation (ZGA). Although the regulation of mRNA translation by poly(A) tail length plays an important role in the mammalian OET, the dynamics and functions of non-A residues in poly(A) tails are completely unknown. In this study, we profiled the genome-wide presence, abundance, and roles of non-A residues during the OET in mice using PAIso-seq1 and PAIso-seq, two complementary methods of poly(A) tail analysis. We found that non-A residues are highly dynamic in maternal mRNA, following a general pattern of beginning to increase at the MII stage, becoming highly abundant after fertilization with U residues in about half of poly(A) tails in 1-cell embryos, and declining in 2-cell embryos. We revealed that Btg4-mediated global maternal mRNA deadenylation created the substrates for U residue addition by Tut4/7 at their 3-ends and further re-polyadenylation. In addition, G residues can be added by Tent4a/b. Finally, we demonstrate that G residues stabilize the modified mRNA, while the U residues mark maternal RNA for faster degradation in 2-cell mouse embryos. Taken together, these findings demonstrate that non-A residues are abundant and re-sculpt the maternal transcriptome to initiate zygotic development, which reveals the functional importance of the post-transcriptional regulation mediated by non-A residues in mRNA poly(A) tails.

RNA degradation sculpts the maternal transcriptome during Drosophila oogenesis

In sexually reproducing animals, the oocyte contributes a large supply of RNAs that are essential to launch development upon fertilization. The mechanisms that regulate the composition of the maternal RNA contribution during oogenesis are unclear. Here, we show that a subset of RNAs expressed during the early stages of oogenesis is subjected to regulated degradation during oocyte specification. Failure to remove these RNAs results in oocyte dysfunction and death. We identify the RNA-degrading Super Killer complex and No-Go Decay factor Pelota as key regulators of oogenesis via targeted clearance of RNAs expressed in germline stem cells. These regulators target RNAs enriched for cytidine sequences bound by the protein Half pint. Thus, RNA degradation helps orchestrate a germ cell-to-maternal transition by sculpting the maternal RNA contribution to the zygote.