Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression
Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression
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DOI：
10.1093/hmg/11.24.3007
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发表时间：
2002-11-15
影响因子：
3.5
通讯作者：
Khandjian, EW
中科院分区：
文献类型：
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作者：
Mazroui, R;Huot, ME;Khandjian, EW
脆性X智力低下蛋白（FMRP），一种RNA结合蛋白的缺乏，是脆性X综合征的原因，这是遗传性智力低下的最常见形式。FMRP是与含有poly（A）+mRNA的mRNP复合物相关的胞质蛋白。作为理解FMRP功能的一步，我们建立了永生STEK Fmr1 KO细胞系，并通过FMR1表达载体的转染试验显示，新合成的FMRP积累到细胞质颗粒中。这些结构包含mRNA和其他几种RNA结合蛋白。这些细胞质颗粒的形成依赖于位于RGG结构域的决定簇。我们还提供了证据表明，FMRP作为一个翻译阻遏物与报告基因共转染后。含有FMRP的mRNP是在多聚核糖体和细胞质颗粒之间振荡的动态结构，使人联想到含有抑制的mRNA的应激颗粒。我们推测，在神经元中，FMRP在不称职的mRNP颗粒中起着mRNA阻遏物的作用，这些颗粒必须从细胞体易位到远端位置，如树突棘和突触体。
Absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein, is responsible for the Fragile X syndrome, the most common form of inherited mental retardation. FMRP is a cytoplasmic protein associated with mRNP complexes containing poly(A)+mRNA. As a step towards understanding FMRP function(s), we have established the immortal STEK Fmr1 KO cell line and showed by transfection assays with FMR1-expressing vectors that newly synthesized FMRP accumulates into cytoplasmic granules. These structures contain mRNAs and several other RNA-binding proteins. The formation of these cytoplasmic granules is dependent on determinants located in the RGG domain. We also provide evidence that FMRP acts as a translation repressor following co-transfection with reporter genes. The FMRP-containing mRNPs are dynamic structures that oscillate between polyribosomes and cytoplasmic granules reminiscent of the Stress Granules that contain repressed mRNAs. We speculate that, in neurons, FMRP plays a role as a mRNA repressor in incompetent mRNP granules that have to be translocated from the cell body to distal locations such as dendritic spines and synaptosomes.