Charlesworth A, Welk J, MacNicol A M
Department of Medicine, Committee on Developmental Biology, Ben May Institute for Cancer Research, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
Dev Biol. 2000 Nov 15;227(2):706-19. doi: 10.1006/dbio.2000.9922.
The Wee1 protein tyrosine kinase is a key regulator of cell cycle progression. Wee1 activity is necessary for the control of the first embryonic cell cycle following the fertilization of meiotically mature Xenopus oocytes. Wee1 mRNA is present in immature oocytes, but Wee1 protein does not accumulate in immature oocytes or during the early stages of progesterone-stimulated maturation. This delay in Wee1 translation is critical since premature Wee1 protein accumulation has been shown to inhibit oocyte maturation. In this study we provide evidence that Wee1 protein accumulation is regulated at the level of mRNA translation. This translational control is directed by sequences within the Wee1 mRNA 3'-untranslated region (3' UTR). Specifically, cytoplasmic polyadenylation element (CPE) sequences within the Wee1 3' UTR are necessary for full translational repression in immature oocytes. Our data further indicate that while CPE-independent mechanisms may regulate the levels of Wee1 protein accumulation during progesterone-stimulated oocyte maturation, the timing of Wee1 mRNA translational induction is directed through a CPE-dependent mechanism.
Wee1蛋白酪氨酸激酶是细胞周期进程的关键调节因子。在减数分裂成熟的非洲爪蟾卵母细胞受精后的首个胚胎细胞周期控制中,Wee1活性是必需的。Wee1 mRNA存在于未成熟卵母细胞中,但Wee1蛋白在未成熟卵母细胞中或在孕酮刺激的成熟早期阶段不会积累。Wee1翻译的这种延迟至关重要,因为过早的Wee1蛋白积累已被证明会抑制卵母细胞成熟。在本研究中,我们提供证据表明Wee1蛋白积累在mRNA翻译水平受到调控。这种翻译控制由Wee1 mRNA 3'非翻译区(3'UTR)内的序列指导。具体而言,Wee1 3'UTR内的细胞质聚腺苷酸化元件(CPE)序列对于未成熟卵母细胞中的完全翻译抑制是必需的。我们的数据进一步表明,虽然不依赖CPE的机制可能在孕酮刺激的卵母细胞成熟过程中调节Wee1蛋白积累水平,但Wee1 mRNA翻译诱导的时间是通过依赖CPE的机制指导的。