Mazroui Rachid, Huot Marc-Etienne, Tremblay Sandra, Filion Christine, Labelle Yves, Khandjian Edouard W
Unité de Recherche en Génétique Humaine et Moléculaire, Centre de recherche Hôpital Saint François d'Assise, 10 rue de l'Espinay, Québec G1L 3L5, PQ, Canada.
Hum Mol Genet. 2002 Nov 15;11(24):3007-17. doi: 10.1093/hmg/11.24.3007.
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.
脆性X智力低下蛋白（FMRP）是一种RNA结合蛋白，其缺失会导致脆性X综合征，这是遗传性智力低下最常见的形式。FMRP是一种与含有多聚腺苷酸（poly(A)+）mRNA的mRNP复合物相关的细胞质蛋白。作为理解FMRP功能的第一步，我们建立了永生化的STEK Fmr1基因敲除细胞系，并通过用表达FMR1的载体进行转染实验表明，新合成的FMRP会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取决于位于RGG结构域的决定因素。我们还提供证据表明，与报告基因共转染后，FMRP作为翻译抑制因子发挥作用。含有FMRP的mRNP是动态结构，在多核糖体和细胞质颗粒之间振荡，这让人联想到含有被抑制mRNA的应激颗粒。我们推测，在神经元中，FMRP在功能不全的mRNP颗粒中作为mRNA抑制因子发挥作用，这些颗粒必须从细胞体转运到远端位置，如树突棘和突触小体。
