Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8197, 75230 Paris Cedex 05, France.
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5903-8. doi: 10.1073/pnas.1218732110. Epub 2013 Mar 25.
The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonucleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.
多蛋白外显子结合复合体（EJC）由剪接机制沉积，是信使核糖核蛋白颗粒的重要组成部分，因为它通过无意义介导的 mRNA 降解途径参与 mRNA 生命周期从剪接到监控的许多步骤。通过未知的机制，EJC 还刺激新合成的 mRNA 的翻译效率。在这里，我们表明，在四个 EJC 核心成分中，RNA 结合蛋白转移性淋巴结 51（MLN51）是翻译增强子。MLN51 的过表达通过 EJC 优先增加含内含子的报告基因的翻译，而沉默 MLN51 则降低翻译。此外，细胞游离翻译提取物中 MLN51 水平的调节证实了其在蛋白质合成中的直接作用。免疫沉淀表明 MLN51 与起始因子和核糖体亚基结合，体外结合测定表明 MLN51 单独或作为 EJC 的一部分与关键的真核翻译起始因子 eIF3 直接相互作用。总之，我们的数据将 MLN51 定义为连接 EJC 和翻译机制的翻译激活剂。
