Charlesworth Amanda, Wilczynska Anna, Thampi Prajitha, Cox Linda L, MacNicol Angus M
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
EMBO J. 2006 Jun 21;25(12):2792-801. doi: 10.1038/sj.emboj.7601159. Epub 2006 Jun 8.
A strict temporal order of maternal mRNA translation is essential for meiotic cell cycle progression in oocytes of the frog Xenopus laevis. The molecular mechanisms controlling the ordered pattern of mRNA translational activation have not been elucidated. We report a novel role for the neural stem cell regulatory protein, Musashi, in controlling the translational activation of the mRNA encoding the Mos proto-oncogene during meiotic cell cycle progression. We demonstrate that Musashi interacts specifically with the polyadenylation response element in the 3' untranslated region of the Mos mRNA and that this interaction is necessary for early Mos mRNA translational activation. A dominant inhibitory form of Musashi blocks maternal mRNA cytoplasmic polyadenylation and meiotic cell cycle progression. Our data suggest that Musashi is a target of the initiating progesterone signaling pathway and reveal that late cytoplasmic polyadenylation element-directed mRNA translation requires early, Musashi-dependent mRNA translation. These findings indicate that Musashi function is necessary to establish the temporal order of maternal mRNA translation during Xenopus meiotic cell cycle progression.
严格的母源mRNA翻译时间顺序对于非洲爪蟾卵母细胞减数分裂细胞周期的进程至关重要。控制mRNA翻译激活有序模式的分子机制尚未阐明。我们报道了神经干细胞调节蛋白Musashi在减数分裂细胞周期进程中控制编码Mos原癌基因的mRNA翻译激活方面的新作用。我们证明Musashi与Mos mRNA 3'非翻译区的聚腺苷酸化反应元件特异性相互作用，并且这种相互作用对于早期Mos mRNA翻译激活是必需的。Musashi的显性抑制形式会阻断母源mRNA的细胞质聚腺苷酸化和减数分裂细胞周期进程。我们的数据表明Musashi是起始孕酮信号通路的一个靶点，并揭示晚期细胞质聚腺苷酸化元件指导的mRNA翻译需要早期的、依赖Musashi的mRNA翻译。这些发现表明，在非洲爪蟾减数分裂细胞周期进程中，Musashi功能对于建立母源mRNA翻译的时间顺序是必要的。
