EJC core component MLN51 interacts with elF3 and activates translation
EJC core component MLN51 interacts with elF3 and activates translation
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DOI：
10.1073/pnas.1218732110
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发表时间：
2013-04-09
影响因子：
11.1
通讯作者：
Le Hir, Herve
中科院分区：
文献类型：
--
作者：
Chazal, Pierre-Etienne;Daguenet, Elisabeth;Le Hir, Herve
由剪接机制沉积的多蛋白外显子连接复合物（EJC）是信使核糖核蛋白颗粒的重要组成部分，因为它通过无义介导的mRNA衰变途径参与mRNA生命周期中从剪接到监视的许多步骤。通过一种未知的机制，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核心组件，RNA结合蛋白转移淋巴结51（MLN51）是一个翻译增强子。MLN51的过表达优先通过EJC增加含有内含子的报告基因的翻译，而沉默MLN51减少翻译。此外，无细胞翻译提取物中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与转录起始因子和核糖体亚基相关，体外结合试验表明，MLN51单独或作为EJC的一部分，直接与关键的真核翻译起始因子eIF3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。
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 elF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.