I-52: Maternal mRNA Metabolism duringOocyte-to-Zygote Transition

Background: Maternal mRNA degradation is a selective process that occurs in waves corresponding to important developmental transitions such as resumption of meiosis, fertilization and zygotic genome activation. It has been demonstrated that the number, position, and combination of 3 UTR cis-acting elements interacting with trans-acting protein factors regulate translation and mRNA stability. Our goal is to integrate bioinformatic analysis of microarray expression data and experimental analysis of mechanisms underlying control of maternal mRNA degradation. Materials and Methods: Bioinformatic analysis of microarray expression data from oocytes and early embryos, knock-down of candidates regulating maternal mRNA stability, and biochemical analysis of the role of candidates in reporter assays in cell culture.Results: We found that the decapping complex is strongly upregulated during resumption of meiosis. Our analysis of microarray expression data from oocytes has revealed that the length of 3 UTR inversely correlates with mRNA degradation during meiosis. Furthermore, analysis of 3 UTR composition of maternal mRNAs has disclosed that AU-rich motifs are strongly associated with meiotic transcriptome remodelling. While U-rich elements were predominantly present in naturally unstable transcripts in oocytes, several AU-rich motifs were significantly enriched in mRNAs that are rather stable during meiotic maturation. To get more insight into underlying mechanisms, we analyzed expression of >20 genes encodingproteins binding AU-rich sequences. We found that Elavl2 expression is enhanced in the oocyte relative to somatic tissues (except of neurons). ELAVL2 is an excellent candidate for a maternal factor stabilizing maternal mRNAs during meiotic maturation. Effects of the loss of ELAVL2 on the oocyte-to-zygote transition are currently under investigation. Conclusion: Maternal mRNA degradation occurs in phases and the first wave maternal mRNA degradation during meiotic maturation appears to be composed of selective mRNA stabilization during global upregulation of mRNA degradation.