Cap-dependent translational inhibition establishes two opposing morphogen gradients in Drosophila embryos
Cap-dependent translational inhibition establishes two opposing morphogen gradients in Drosophila embryos
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DOI：
10.1016/j.cub.2006.08.093
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发表时间：
2006-10-24
期刊：
影响因子：
9.2
通讯作者：
Sonenberg, Nahum
中科院分区：
文献类型：
--
作者：
Cho, Park F.;Gamberi, Chiara;Sonenberg, Nahum
在早期果蝇胚胎中，转录因子的不对称分布（由于其母体来源的mRNA的翻译控制而建立）启动了模式形成[1-4]。例如，均匀分布的母体hunchback（hb）mRNA的翻译在后部受到抑制，从而沿纵轴沿着形成前部至后部的蛋白质浓度梯度[5，6]。hb mRNA翻译的抑制需要mRNP复合物（NRE复合物），其由Nanos（Nos）、Pumilio（Pum）和脑肿瘤（Brat）蛋白组成，以及存在于hb mRNA 3' UTR中的Nos响应元件（NRE）[7-9]。负责这种翻译抑制的mRNA 5'效应蛋白的身份仍然难以捉摸。在这里，我们发现d4 EHP，一种抑制尾部（cad）mRNA翻译的帽结合蛋白[110]，也通过与mRNA 5'帽结构（m（7）GpppN，其中N是任何核苷酸）[11]和Brat同时相互作用来抑制hb mRNA翻译。因此，通过调节Cad和Hb的表达，d4 EHP在果蝇胚胎中建立前后轴极性中起着关键作用。
In the early Drosophila embryo, asymmetric distribution of transcription factors, established as a consequence of translational control of their maternally derived mRNAs, initiates pattern formation [1-4]. For instance, translation of the uniformly distributed maternal hunchback(hb) mRNA is inhibited at the posterior to form an anterior-to-posterlor protein concentration gradient along the longitudinal axis [5, 6]. Inhibition of hb mRNA translation requires an mRNP complex (the NRE complex), which consists of Nanos (Nos), Pumilio (Pum), and Brain tumor (Brat) proteins, and the Nos responsive element (NRE) present in the 3' UTR of hb mRNA [7-9]. The identity of the mRNA 5' effector protein that is responsible for this translational inhibition remained elusive. Here we show that d4EHP, a cap binding protein that represses caudal (cad) mRNA translation [110], also inhibits hb mRNA translation by interacting simultaneously with the mRNA 5' cap structure (m(7) GpppN, where N is any nucleotide) [11] and Brat. Thus, by regulating Cad and Hb expression, d4EHP plays a key role in establishing anterior-posterior axis polarity in the Drosophila embryo.