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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Animals, Genetically Modified
-
CELF1 Protein
-
Disease Models, Animal
-
Drosophila
-
Drosophila Proteins / genetics
-
Drosophila Proteins / metabolism*
-
Eye / pathology
-
Eye / ultrastructure
-
Fragile X Mental Retardation Protein / genetics
-
Fragile X Syndrome / complications
-
Fragile X Syndrome / genetics*
-
Fragile X Syndrome / pathology
-
Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
-
Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
-
Immunoprecipitation / methods
-
Microscopy, Electron, Scanning / methods
-
Neurodegenerative Diseases / genetics
-
Neurodegenerative Diseases / metabolism*
-
Neurodegenerative Diseases / pathology
-
RNA-Binding Proteins / genetics
-
RNA-Binding Proteins / metabolism*
-
Trinucleotide Repeat Expansion / genetics*
Substances
-
CELF1 Protein
-
CELF1 protein, human
-
Drosophila Proteins
-
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
-
RNA-Binding Proteins
-
Fragile X Mental Retardation Protein