Corbin F, Bouillon M, Fortin A, Morin S, Rousseau F, Khandjian E W
Pavillon Saint-Francois d'Assise du CHUQ, Département de biologie médicale, Faculté de médecine, Université Laval, Québec, Canada.
Hum Mol Genet. 1997 Sep;6(9):1465-72. doi: 10.1093/hmg/6.9.1465.
The fragile X syndrome results from a transcriptional silencing of the FMR1 gene and the absence of its encoded protein. FMRP is a cytoplasmic RNA-binding protein, whose specific cellular function is still unknown. We present evidence that virtually all detectable cytoplasmic FMRP in mouse NIH 3T3 and human HeLa cells is found strictly in association with mRNA in actively translating polyribosomes. Furthermore, FMRP released from polyribosomes is associated with ribonucleoprotein complexes with sedimentation coefficients of 60-70S and selection on oligo(dT)-cellulose reveals that this association is specific to poly(A)-containing mRNPs. This association with actively translating polyribosomes is not affected by alteration of translational processes induced by serum stimulation and starvation in NIH 3T3 cells, suggesting that FMR1 expression is not cell cycle regulated and that FMRP might have a house-keeping function. FXR2 protein, which is closely related to FMRP, is also detected associated with mRNPs in translating polyribosomes. The results strongly suggest that FMRP might be a mRNA chaperone interacting with mRNP complexes.
脆性X综合征是由FMR1基因的转录沉默及其编码蛋白的缺失所致。FMRP是一种细胞质RNA结合蛋白，其具体的细胞功能尚不清楚。我们提供的证据表明，在小鼠NIH 3T3细胞和人HeLa细胞中，几乎所有可检测到的细胞质FMRP都严格与活跃翻译的多核糖体中的mRNA相关联。此外，从多核糖体释放的FMRP与沉降系数为60 - 70S的核糖核蛋白复合物相关联，并且在寡聚（dT）-纤维素上的筛选表明这种关联对含聚腺苷酸的mRNA特异。在NIH 3T3细胞中，这种与活跃翻译的多核糖体的关联不受血清刺激和饥饿诱导的翻译过程改变的影响，这表明FMR1表达不受细胞周期调节，并且FMRP可能具有管家功能。与FMRP密切相关的FXR2蛋白也被检测到与翻译多核糖体中的mRNA特异相关。这些结果强烈表明FMRP可能是一种与mRNA特异相关的mRNA伴侣蛋白。
