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

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.

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*


  • CELF1 Protein
  • CELF1 protein, human
  • Drosophila Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein