Benoit Béatrice, Mitou Géraldine, Chartier Aymeric, Temme Claudia, Zaessinger Sophie, Wahle Elmar, Busseau Isabelle, Simonelig Martine
Génétique du Développement de la Drosophila, Institut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier Cedex 5, France.
Dev Cell. 2005 Oct;9(4):511-22. doi: 10.1016/j.devcel.2005.09.002.
Translational control of maternal mRNA through regulation of poly(A) tail length is crucial during early development. The nuclear poly(A) binding protein, PABP2, was identified biochemically from its role in nuclear polyadenylation. Here, we analyze the in vivo function of PABP2 in Drosophila. PABP2 is required in vivo for polyadenylation, and Pabp2 function, including poly(A) polymerase stimulation, is essential for viability. We also demonstrate an unanticipated cytoplasmic function for PABP2 during early development. In contrast to its role in nuclear polyadenylation, cytoplasmic PABP2 acts to shorten the poly(A) tails of specific mRNAs. PABP2, together with the deadenylase CCR4, regulates the poly(A) tails of oskar and cyclin B mRNAs, both of which are also controlled by cytoplasmic polyadenylation. Both Cyclin B protein levels and embryonic development depend upon this regulation. These results identify a regulator of maternal mRNA poly(A) tail length and highlight the importance of this mode of translational control.
通过调控多聚腺苷酸(poly(A))尾长度对母体mRNA进行翻译控制在早期发育过程中至关重要。核多聚腺苷酸结合蛋白PABP2是通过其在核多聚腺苷酸化中的作用经生化方法鉴定出来的。在此,我们分析了果蝇中PABP2的体内功能。PABP2在体内对于多聚腺苷酸化是必需的,并且Pabp2的功能,包括对多聚(A)聚合酶的刺激,对于生存能力至关重要。我们还证明了PABP2在早期发育过程中具有意想不到的细胞质功能。与其在核多聚腺苷酸化中的作用相反,细胞质中的PABP2起到缩短特定mRNA的多聚(A)尾的作用。PABP2与去腺苷酸化酶CCR4一起,调节osk和细胞周期蛋白B mRNA的多聚(A)尾,这两种mRNA也受细胞质多聚腺苷酸化的控制。细胞周期蛋白B的蛋白水平和胚胎发育均依赖于这种调控。这些结果鉴定出了一种母体mRNA多聚(A)尾长度的调节因子,并突出了这种翻译控制模式的重要性。