RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS

Sofola, Oyinkan, Jin, Peng, Qin, Yunlong, Duan, Ranhui, Liu, Huijie, de Haro, Maria, Nelson, David and Botas, Juan (2007) RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron, 55 (4). pp. 565-571. ISSN 0896-6273 (Accepted)

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Oyinkan Adesakin
Date Deposited: 02 Nov 2017 09:48
Last Modified: 02 Nov 2017 09:48
URI: http://sro.sussex.ac.uk/id/eprint/70853

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