RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS.
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.
Sofola
Oyinkan A
OA
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jin
Peng
P
Qin
Yunlong
Y
Duan
Ranhui
R
Liu
Huijie
H
de Haro
Maria
M
Nelson
David L
DL
Botas
Juan
J
D000818:Animals; D030801:Animals, Genetically Modified; D000067879:CELF1 Protein; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000473:pathology / Q000648:ultrastructure; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D000067879:CELF1 Protein; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D016601:RNA-Binding Proteins; C102843:CELF1 protein, human
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