Poly(A)尾介导母源性TCL1表达参与调控卵母细胞质量的机制研究

基因表达模式从卵母细胞基因向早期胚胎的基因转换，是早期胚胎发育过程中的第一个关键事件，涉及到大量母源mRNA的降解与翻译。其中，Poly(A)尾长度的控制是一种重要的转录后修饰，参与调节RNA稳定性以及翻译活性。基于自主开发的PACTome-seq技术，鉴定出在受精卵中仍维持较长Poly(A)尾的潜在母源基因。筛选了人和小鼠保守的母源基因Tcl1。发现Tcl1在高龄卵母细胞中表达下降，Poly(A)尾也变短，提示Tcl1的低表达或异常Poly(A)尾可能暗示着卵母细胞的低质量。进一步基于Tcl1敲除小鼠模型，应用免疫荧光、免疫沉淀、RNA-seq等技术，探究Tcl1对于卵母细胞成熟及胚胎早期发育过程的影响。寻找与TCL1相互作用的分子，深入探讨其作用机制。本研究不仅能揭示母源基因TCL1调节卵母细胞成熟及早期胚胎发育潜能的机制，而且对于提高卵母细胞质量也具有潜在的指导意义。

Maternal-to-zygotic transition (MZT) is an initial step in the early development of all investigated animal species involved maternal mRNA clearance and translation. The control of Poly(A) tail length is an important post-transcriptional modification involved in regulating RNA stability as well as translational activity. Based on the developed PACTome-seq, we revealed the dynamic landscape of Poly(A) tail lengths in mouse gametes and preimplantation embryos of different developmental stages. We identified a fraction of genes that still maintain a long Poly(A) tail after fertilization, which may be potential maternal effect genes. We focused on Tcl1, a maternal effect gene with a consistent trend of Poly(A) tail in human and mice. We revealed the specific factors of Tcl1 deletion affecting oocyte quality through further analysis of oocyte maturation and early embryonic development in Tcl1 knockout mouse model. Immunofluorescence, immunoprecipitation and RNA-seq techniques will be applied to find the molecules interacting with TCL1 and to explore its mechanism in depth. This study not only reveals the mechanism of maternal factor TCL1 regulating oocyte cytoplasmic maturation, but also has potential implications for improving oocyte quality and embryonic developmental potential.