Sofola Oyinkan A, Jin Peng, Qin Yunlong, Duan Ranhui, Liu Huijie, de Haro Maria, Nelson David L, Botas Juan
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Neuron. 2007 Aug 16;55(4):565-71. doi: 10.1016/j.neuron.2007.07.021.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described neurodegenerative disorder of older adult carriers of premutation alleles (60-200 CGG repeats) in the fragile X mental retardation gene (FMR1). It has been proposed that FXTAS is an RNA-mediated neurodegenerative disease caused by the titration of RNA-binding proteins by the CGG repeats. To test this hypothesis, we utilize a transgenic Drosophila model of FXTAS that expresses a premutation-length repeat (90 CGG repeats) from the 5' UTR of the human FMR1 gene and displays neuronal degeneration. Here, we show that overexpression of RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppresses the phenotype of the CGG transgenic fly. Furthermore, we show that hnRNP A2/B1 directly interacts with riboCGG repeats and that the CUGBP1 protein interacts with the riboCGG repeats via hnRNP A2/B1.
脆性X相关震颤/共济失调综合征（FXTAS）是一种最近被描述的神经退行性疾病，发生于脆性X智力低下基因（FMR1）前突变等位基因（60 - 200个CGG重复序列）的老年携带者。有人提出，FXTAS是一种由CGG重复序列滴定RNA结合蛋白引起的RNA介导的神经退行性疾病。为了验证这一假设，我们利用了一种FXTAS的转基因果蝇模型，该模型从人类FMR1基因的5' UTR表达前突变长度的重复序列（90个CGG重复序列），并表现出神经元变性。在这里，我们表明RNA结合蛋白hnRNP A2/B1和CUGBP1的过表达抑制了CGG转基因果蝇的表型。此外，我们表明hnRNP A2/B1直接与核糖CGG重复序列相互作用，并且CUGBP1蛋白通过hnRNP A2/B1与核糖CGG重复序列相互作用。
