Prasad C Krishna, Mahadevan Mahendran, MacNicol Melanie C, MacNicol Angus M
Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Mol Reprod Dev. 2008 Aug;75(8):1258-68. doi: 10.1002/mrd.20877.
The Mos proto-oncogene is a critical regulator of vertebrate oocyte maturation. The maturation-dependent translation of Mos protein correlates with the cytoplasmic polyadenylation of the maternal Mos mRNA. However, the precise temporal requirements for Mos protein function differ between oocytes of model mammalian species and oocytes of the frog Xenopus laevis. Despite the advances in model organisms, it is not known if the translation of the human Mos mRNA is also regulated by cytoplasmic polyadenylation or what regulatory elements may be involved. We report that the human Mos 3' untranslated region (3' UTR) contains a functional cytoplasmic polyadenylation element (CPE) and demonstrate that the endogenous Mos mRNA undergoes maturation-dependent cytoplasmic polyadenylation in human oocytes. The human Mos 3' UTR interacts with the human CPE-binding protein and exerts translational control on a reporter mRNA in the heterologous Xenopus oocyte system. Unlike the Xenopus Mos mRNA, which is translationally activated by an early acting Musashi/polyadenylation response element (PRE)-directed control mechanism, the translational activation of the human Mos 3' UTR is dependent on a late acting CPE-dependent process. Taken together, our findings suggest a fundamental difference in the 3' UTR regulatory mechanisms controlling the temporal induction of maternal Mos mRNA polyadenylation and translational activation during Xenopus and mammalian oocyte maturation.
Mos原癌基因是脊椎动物卵母细胞成熟的关键调节因子。Mos蛋白的成熟依赖性翻译与母体Mos mRNA的细胞质聚腺苷酸化相关。然而,模型哺乳动物物种的卵母细胞与非洲爪蟾的卵母细胞对Mos蛋白功能的精确时间要求有所不同。尽管在模式生物方面取得了进展,但尚不清楚人类Mos mRNA的翻译是否也受细胞质聚腺苷酸化调节,以及可能涉及哪些调节元件。我们报告称,人类Mos 3'非翻译区(3'UTR)包含一个功能性细胞质聚腺苷酸化元件(CPE),并证明内源性Mos mRNA在人类卵母细胞中经历成熟依赖性细胞质聚腺苷酸化。人类Mos 3'UTR与人类CPE结合蛋白相互作用,并在异源爪蟾卵母细胞系统中对报告基因mRNA施加翻译控制。与通过早期作用的武藏/聚腺苷酸化反应元件(PRE)导向的控制机制激活翻译的爪蟾Mos mRNA不同,人类Mos 3'UTR的翻译激活依赖于晚期作用的CPE依赖性过程。综上所述,我们的研究结果表明,在爪蟾和哺乳动物卵母细胞成熟过程中,控制母体Mos mRNA聚腺苷酸化和翻译激活时间诱导的3'UTR调节机制存在根本差异。