Nakamura Akira, Sato Keiji, Hanyu-Nakamura Kazuko
Laboratory for Germline Development, Riken Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
Dev Cell. 2004 Jan;6(1):69-78. doi: 10.1016/s1534-5807(03)00400-3.
Translational control is a critical process in the spatio-temporal restriction of protein production. In Drosophila oogenesis, translational repression of oskar (osk) RNA during its localization to the posterior pole of the oocyte is essential for embryonic patterning and germ cell formation. This repression is mediated by the osk 3' UTR binding protein Bruno (Bru), but the underlying mechanism has remained elusive. Here, we report that an ovarian protein, Cup, is required to repress precocious osk translation. Cup binds the 5'-cap binding translation initiation factor eIF4E through a sequence conserved among eIF4E binding proteins. A mutant Cup protein lacking this sequence fails to repress osk translation in vivo. Furthermore, Cup interacts with Bru in a yeast two-hybrid assay, and the Cup-eIF4E complex associates with Bru in an RNA-independent manner. These results suggest that translational repression of osk RNA is achieved through a 5'/3' interaction mediated by an eIF4E-Cup-Bru complex.
翻译控制是蛋白质产生的时空限制中的一个关键过程。在果蝇卵子发生过程中，oskar（osk）RNA在定位于卵母细胞后极期间的翻译抑制对于胚胎模式形成和生殖细胞形成至关重要。这种抑制由osk 3'UTR结合蛋白布鲁诺（Bru）介导，但潜在机制仍不清楚。在这里，我们报告一种卵巢蛋白Cup是抑制过早的osk翻译所必需的。Cup通过eIF4E结合蛋白中保守的序列与5'-帽结合翻译起始因子eIF4E结合。缺乏该序列的突变Cup蛋白在体内无法抑制osk翻译。此外，在酵母双杂交试验中，Cup与Bru相互作用，并且Cup-eIF4E复合物以不依赖RNA的方式与Bru结合。这些结果表明，osk RNA的翻译抑制是通过由eIF4E-Cup-Bru复合物介导的5'/3'相互作用实现的。
