Nuclear Accumulation of Stress Response mRNAs Contributes to the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats
Nuclear Accumulation of Stress Response mRNAs Contributes to the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder seen in Fragile X premutation carriers. Previous studies found that Fragile X rCGG repeats are sufficient to cause neurodegeneration and that the rCGG repeat-binding proteins Pur α and hnRNP A2/B1 can modulate rCGG-mediated neuronal toxicity. To explore the role of Pur α in rCGG-mediated neurodegeneration further, we took a proteomic approach and identified more than 100 proteins that interact with Pur α. Of particular interest is Rm62, the Drosophila ortholog of p68 RNA helicase, which could modulate rCGG-mediated neurodegeneration. Here we show that rCGG repeats decreased the expression of Rm62 posttranscriptionally, leading to the nuclear accumulation of Hsp70 transcript, as well as additional mRNAs involved in stress and immune responses. Together these findings suggest that abnormal nuclear accumulation of these mRNAs, likely as a result of impaired nuclear export, could contribute to FXTAS pathogenesis.
- Emory University United States
- Pacific Northwest National Laboratory United States
- Emory University School of Medicine United States
- EMORY UNIVERSITY
- Emory University School of Medicine United States
Cell Nucleus, Neurons, QH426-470, DNA-Binding Proteins, Fragile X Mental Retardation Protein, Fragile X Syndrome, Mutation, Nerve Degeneration, Genetics, Animals, Drosophila Proteins, Drosophila, HSP70 Heat-Shock Proteins, RNA, Messenger, Trinucleotide Repeat Expansion, Research Article, Transcription Factors
Cell Nucleus, Neurons, QH426-470, DNA-Binding Proteins, Fragile X Mental Retardation Protein, Fragile X Syndrome, Mutation, Nerve Degeneration, Genetics, Animals, Drosophila Proteins, Drosophila, HSP70 Heat-Shock Proteins, RNA, Messenger, Trinucleotide Repeat Expansion, Research Article, Transcription Factors
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