PABPN1 promotes meiotic maturation of oocytes by interacting with PAPOLA

Poly(A) polymerase α (PAPα), as the specific mRNA polyadenylation enzyme in the cytoplasm of mammalian oocytes, is essential for oocytes to exclude the first polar body. However, PAPα knockout did not affect germinal vesicles breakdown (GVBD) of oocytes, and the mechanism needs to be further explored. In this study, we identified that PAPα work together with poly(A)-bound RNA binding protein PABPN1 to promote the rupture of germinal vesicles in mammalian oocytes. The protein level of Pabpn1 gradually increases with the meiotic maturation of oocytes. The oocytes specifically knocked out Pabpn1 at the primary follicle stage could develop into the fully grown (FGO) stage, but hardly could enter into the meiotic process. The activated form of CDK1 was injected into Pabpn1-null oocytes, the oocytes could enter into meiotic process. The translational activity of Pabpn1-null oocytes was significantly lower than that of wild-type oocytes during meiosis. In particular, the expression level of protein (BTG4 and CDC25), which were essential for the meiotic maturation of oocytes, were significantly decreased. Therefore, during the oocyte meiosis process, PABPN1 and PAPα jointly promote the oocyte to enter the meiosis process. Examination of WT and Pabpn1-null transcriptome in oocytes

聚腺苷酸聚合酶α（Poly(A) polymerase α, PAPα）作为哺乳动物卵母细胞细胞质中特异性的mRNA多聚腺苷酸化酶，对卵母细胞排出第一极体至关重要。然而，PAPα敲除并不会影响卵母细胞的生发泡破裂（germinal vesicles breakdown, GVBD），其具体调控机制尚待进一步阐明。本研究证实，PAPα可与聚腺苷酸结合RNA结合蛋白PABPN1协同作用，促进哺乳动物卵母细胞的生发泡破裂。Pabpn1的蛋白表达水平随卵母细胞减数分裂成熟进程逐步升高。在初级卵泡阶段特异性敲除Pabpn1的卵母细胞，虽可发育至完全成熟卵母细胞（fully grown oocyte, FGO）阶段，但几乎无法进入减数分裂进程。将活化型细胞周期蛋白依赖性激酶1（CDK1）注射至Pabpn1敲除卵母细胞后，该类卵母细胞可重新进入减数分裂进程。减数分裂期间，Pabpn1敲除卵母细胞的翻译活性显著低于野生型卵母细胞。尤为关键的是，对卵母细胞减数分裂成熟至关重要的BTG4与CDC25的蛋白表达水平显著下调。综上，在卵母细胞减数分裂过程中，PABPN1与PAPα协同促进卵母细胞进入减数分裂程序。对野生型及Pabpn1敲除卵母细胞的转录组进行检测。