Welk J F, Charlesworth A, Smith G D, MacNicol A M
Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Gene. 2001 Jan 24;263(1-2):113-20. doi: 10.1016/s0378-1119(00)00588-6.
The maturation of human oocytes occurs in the absence of gene transcription. In model organisms, such as Drosophila, Xenopus, and the mouse, oocyte maturation and early pattern formation is mediated through the regulated translation of maternally derived mRNAs. The maturation-dependent stimulation of maternal mRNA translation is correlated with increases in poly(A) tail length, controlled through a process termed cytoplasmic polyadenylation. However, this mechanism of mRNA translational control has not been characterized in humans. In this study we report the cloning of a human cytoplasmic polyadenylation element binding (hCPEB) protein with sequence-specific RNA binding activity. Our data demonstrate that alternative splicing generates hCPEB mRNAs that encode proteins with a conserved C-terminal RNA binding domain but with different N-terminal regulatory domains. The hCPEB mRNA is expressed in the brain and heart as well as in immature oocytes, consistent with the hypothesis that cytoplasmic polyadenylation may regulate the translation of human mRNAs in both oocytes and somatic cells.
人类卵母细胞的成熟过程在没有基因转录的情况下发生。在果蝇、非洲爪蟾和小鼠等模式生物中,卵母细胞成熟和早期模式形成是通过母源mRNA的翻译调控来介导的。母源mRNA翻译的成熟依赖性刺激与多聚腺苷酸(poly(A))尾巴长度的增加相关,这一过程通过称为细胞质聚腺苷酸化的过程来控制。然而,这种mRNA翻译控制机制在人类中尚未得到表征。在本研究中,我们报告了一种具有序列特异性RNA结合活性的人类细胞质聚腺苷酸元件结合(hCPEB)蛋白的克隆。我们的数据表明,可变剪接产生了hCPEB mRNA,其编码的蛋白质具有保守的C末端RNA结合结构域,但具有不同的N末端调节结构域。hCPEB mRNA在大脑、心脏以及未成熟卵母细胞中表达,这与细胞质聚腺苷酸化可能在卵母细胞和体细胞中调节人类mRNA翻译的假设一致。