Department of Biology, McGill University, Montreal, Quebec, Canada.
Mol Cell Biol. 2013 Aug;33(15):2854-64. doi: 10.1128/MCB.01354-12. Epub 2013 May 28.
Translation is a fundamental step in gene expression, and translational control is exerted in many developmental processes. Most eukaryotic mRNAs are translated by a cap-dependent mechanism, which requires recognition of the 5'-cap structure of the mRNA by eukaryotic translation initiation factor 4E (eIF4E). eIF4E activity is controlled by eIF4E-binding proteins (4E-BPs), which by competing with eIF4G for eIF4E binding act as translational repressors. Here, we report the discovery of Mextli (Mxt), a novel Drosophila melanogaster 4E-BP that in sharp contrast to other 4E-BPs, has a modular structure, binds RNA, eIF3, and several eIF4Es, and promotes translation. Mxt is expressed at high levels in ovarian germ line stem cells (GSCs) and early-stage cystocytes, as is eIF4E-1, and we demonstrate the two proteins interact in these cells. Phenotypic analysis of mxt mutants indicates a role for Mxt in germ line stem cell (GSC) maintenance and in early embryogenesis. Our results support the idea that Mxt, like eIF4G, coordinates the assembly of translation initiation complexes, rendering Mxt the first example of evolutionary convergence of eIF4G function.
翻译是基因表达的基本步骤,翻译调控在许多发育过程中发挥作用。大多数真核生物的 mRNA 通过帽依赖机制进行翻译,该机制需要真核翻译起始因子 4E(eIF4E)识别 mRNA 的 5'-帽结构。eIF4E 的活性受到 eIF4E 结合蛋白(4E-BPs)的控制,这些蛋白通过与 eIF4G 竞争 eIF4E 的结合来作为翻译抑制剂。在这里,我们报告了一种新的果蝇 4E-BP,即 Mextli(Mxt)的发现。与其他 4E-BPs 形成鲜明对比的是,Mxt 具有模块化结构,可结合 RNA、eIF3 和几种 eIF4Es,并促进翻译。Mxt 在卵巢生殖干细胞(GSCs)和早期囊泡细胞中表达水平很高,与 eIF4E-1 一样,我们证明这两种蛋白质在这些细胞中相互作用。mxt 突变体的表型分析表明 Mxt 在生殖干细胞(GSC)维持和早期胚胎发生中发挥作用。我们的结果支持这样一种观点,即 Mxt 与 eIF4G 一样,协调翻译起始复合物的组装,使 Mxt 成为 eIF4G 功能进化趋同的第一个例子。