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Jin, P., Zarnescu, D.C., Zhang, F., Pearson, C.E., Lucchesi, J.C., Moses, K., Warren, S.T. (2003). RNA-mediated neurodegeneration caused by the Fragile X premutation rCGG repeats in Drosophila.  Neuron 39(5): 739--747.
FlyBase ID
FBrf0162265
Publication Type
Research paper
Abstract

Fragile X syndrome carriers have FMR1 alleles, called premutations, with an intermediate number of 5' untranslated CGG repeats between patients (>200 repeats) and normal individuals (<60 repeats). A novel neurodegenerative disease has recently been appreciated in some premutation carriers. As no neurodegeneration is seen in fragile X patients, who do not express FMR1, we hypothesize that lengthened rCGG repeats of the premutation transcript may lead to neurodegeneration. Here, using Drosophila melanogaster, we show that 90 rCGG repeats alone are sufficient to cause neurodegeneration. This phenotype is neuron specific and rCGG repeat dosage sensitive. Although devoid of mutant protein, this neurodegeneration exhibits neuronal inclusion bodies that are Hsp70 and ubiquitin positive. Overexpression of Hsp70 could suppress the neurodegeneration. These results demonstrate that neurodegenerative phenotype associated with fragile X premutation is indeed caused by the lengthened rCGG repeats and provide the first in vivo experimental demonstration of RNA-mediated neurodegeneration.

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    Language of Publication
    English
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    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neuron
    Title
    Neuron
    Publication Year
    1988-
    ISBN/ISSN
    0896-6273
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