The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif
The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif
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DOI：
10.1093/emboj/20.17.4803
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发表时间：
2001-09-03
期刊：
影响因子：
11.4
通讯作者：
Moine, H
中科院分区：
文献类型：
--
作者：
Schaeffer, C;Bardoni, B;Moine, H
脆性X综合征是由FMRP蛋白的缺失引起的，其功能仍然知之甚少。以前的研究表明，FMRP可能参与mRNA代谢的各个方面，包括运输，稳定性和/或可翻译性。FMRP被证明与脑mRNA的子集以及其自身的mRNA相互作用;然而，没有特异性RNA结合位点可以被精确地识别。在这里，我们报告了一个特定的和高亲和力的FMRP在其自身的mRNA的RGG编码区的结合位点的识别和表征。该位点含有一个嘌呤四联体基序，该基序对FMRP结合是必需的，并且可以被异源四联体形成基序取代。在网织红细胞裂解物中，FMRP与其靶位点的特异性结合通过其抑制在5 '-非翻译区携带RNA靶位点的报告基因的翻译的能力得到进一步证实。我们的数据解决了有趣的问题，FMRP在转录后控制自己的基因和可能的其他靶基因的作用。
Fragile X syndrome is caused by the absence of protein FMRP, the function of which is still poorly understood. Previous studies have suggested that FMRP may be involved in various aspects of mRNA metabolism, including transport, stability, and/or translatability. FMRP was shown to interact with a subset of brain mRNAs as well as with its own mRNA; however, no specific RNA-binding site could be identified precisely. Here, we report the identification and characterization of a specific and high affinity binding site for FMRP in the RGG-coding region of its own mRNA. This site contains a purine quartet motif that is essential for FMRP binding and can be substituted by a heterologous quartet-forming motif. The specific binding of FMRP to its target site was confirmed further in a reticulocyte lysate through its ability to repress translation of a reporter gene harboring the RNA target site in the 5'-untranslated region. Our data address interesting questions concerning the role of FMRP in the post-transcriptional control of its own gene and possibly other target genes.