Control of poly(A)-tail length and translation in vertebrate oocytes and early embryos

During oocyte maturation and early embryonic development, poly(A)-tail lengths strongly influence mRNA translation. However, how tail lengths are controlled at different developmental stages has been unclear. Here, we performed tail-length and translational profiling of mRNA reporter libraries (each with > 10 million 3'-UTR sequence variants) in frog oocytes and embryos, and fish embryos. These analyses revealed that the UUUUA motif specifies cytoplasmic polyadenylation and identified diverse context features that modulate the activity of this 5-mer. Additional sequence motifs drive stage-specific deadenylation in embryos, and UUUUA and C-rich motifs drive tail-length-independent translational repression in oocytes. A neural network model accurately predicts tail-length change during oocyte maturation in frogs, mice, and humans. Analyses of human sequence variants showed that those predicted to disrupt tail-length control have been under negative selection, implying that our insights into control of poly(A)-tail length and translation have implications for human health and fertility. Overall design: Sythetic mRNA reporter libraries with random 3'-UTR sequences under four different sequence contexts were injected into frog oocytes and embryos and fish embryos. Poly(A)-tail lengths were measured to at different developmental stages to examine sequence motifs that caused tail-length changes. At the same time, poly(A)-tail lengths of endogenous mRNAs from frog oocytes and embryos, fish embryos, and mouse oocytes were measured to investiage how their tail lengths were controlled. Please note that sample titles have been updated on Jan 6, 2024.