Association of the breast cancer protein MLN51 with the Exon junction complex via its speckle localizer and RNA binding module
Association of the breast cancer protein MLN51 with the Exon junction complex via its speckle localizer and RNA binding module
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DOI：
10.1074/jbc.m402754200
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发表时间：
2004-08-06
影响因子：
4.8
通讯作者：
Tomasetto, C
中科院分区：
文献类型：
--
作者：
Degot, S;Le Hir, H;Tomasetto, C
MLN51是一种在乳腺癌中过表达的核细胞质穿梭蛋白。哺乳动物中MLN51的功能尚不清楚。它的苍蝇同源物，名为巴伦茨，以及蛋白mago nashi和tsunagi已被证明是oskar mRNA正确定位到卵母细胞后极所必需的。Magoh和Y14是mago nashi和tsunagi的人类同源物，是外显子结复合体（EJC）的核心成分。EJC组装在剪接的mRNA上，并在剪接后的事件中发挥重要作用，包括mRNA输出、无义介导的mRNA衰变和翻译。在本研究中，我们发现人类MLN51是一种存在于核糖核蛋白复合物中的rna结合蛋白。通过共免疫沉淀实验，发现内源性MLN51蛋白与EJC成分相关，包括Magoh、Y14和NFX1/TAP，亚细胞定位研究表明，MLN51在核斑点中与Magoh短暂共定位。此外，我们在共沉淀实验中证明，MLN51在细胞核和细胞质中与剪接的mrna特异性结合，在EJC沉积的位置。最有趣的是，我们在MLN51中发现了一个足以结合RNA，与Magoh和剪接mRNA相互作用，并将蛋白质定位于核斑点的区域。因此，MLN51的这个保守区域被命名为SELOR，代表散斑定位器和RNA结合模块。总之，我们的数据表明，MLN51与细胞核中的EJC相关，并稳定地与细胞质中的mRNA相关，这表明其过表达可能改变癌症中mRNA的代谢。
MLN51 is a nucleocytoplasmic shuttling protein that is overexpressed in breast cancer. The function of MLN51 in mammals remains elusive. Its fly homolog, named barentsz, as well as the proteins mago nashi and tsunagi have been shown to be required for proper oskar mRNA localization to the posterior pole of the oocyte. Magoh and Y14, the human homologs of mago nashi and tsunagi, are core components of the exon junction complex (EJC). The EJC is assembled on spliced mRNAs and plays important roles in post-splicing events including mRNA export, nonsense-mediated mRNA decay, and translation. In the present study, we show that human MLN51 is an RNA-binding protein present in ribonucleoprotein complexes. By co-immunoprecipitation assays, endogenous MLN51 protein is found to be associated with EJC components, including Magoh, Y14, and NFX1/TAP, and subcellular localization studies indicate that MLN51 transiently co-localizes with Magoh in nuclear speckles. Moreover, we demonstrate that MLN51 specifically associates with spliced mRNAs in co-precipitation experiments, both in the nucleus and in the cytoplasm, at the position where the EJC is deposited. Most interesting, we have identified a region within MLN51 sufficient to bind RNA, to interact with Magoh and spliced mRNA, and to address the protein to nuclear speckles. This conserved region of MLN51 was therefore named SELOR for speckle localizer and RNA binding module. Altogether our data demonstrate that MLN51 associates with EJC in the nucleus and remains stably associated with mRNA in the cytoplasm, suggesting that its overexpression might alter mRNA metabolism in cancer.