Abstract：
The human genome has many short tandem repeats, yet the normal functions of these repeats are unclear. The 5\' untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene contains polymorphic CGG repeats, the length of which has differing effects on FMR1 expression and human health, including the neurodevelopmental disorder fragile X syndrome. We deleted the CGG repeats in the FMR1 gene (0CGG) in human stem cells and examined the effects on differentiated neurons. 0CGG neurons have altered subcellular localization of FMR1 mRNA and protein, and differential expression of cellular stress proteins compared with neurons with normal repeats (31CGG). In addition, 0CGG neurons have altered responses to glucocorticoid receptor (GR) activation, including FMR1 mRNA localization, GR chaperone HSP90α expression, GR localization, and cellular stress protein levels. Therefore, the CGG repeats in the FMR1 gene are important for the homeostatic responses of neurons to stress signals.
摘要：
人类基因组有许多短的串联重复序列,然而，这些重复的正常功能尚不清楚。脆性X信使核糖核蛋白1（FMR1）基因的5'非翻译区（UTR）含有多态CGG重复，其长度对FMR1表达和人类健康有不同的影响，包括神经发育障碍脆性X综合征.我们删除了人干细胞中FMR1基因（0CGG）中的CGG重复序列，并检查了对分化神经元的影响。0CGG神经元改变了FMR1mRNA和蛋白的亚细胞定位，与正常重复（31CGG）的神经元相比，细胞应激蛋白的差异表达。此外,0CGG神经元对糖皮质激素受体（GR）激活的反应发生了改变，包括FMR1mRNA定位，GR伴侣HSP90α表达，GR本地化,和细胞应激蛋白水平。因此,FMR1基因中的CGG重复对于神经元对应激信号的稳态反应很重要。
