AI Article Synopsis
- - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder linked to a repeated sequence of CGG in the FMR1 gene, which can lead to two mechanisms of pathology: RNA gain-of-function and production of a harmful protein called FMRpolyG.
- - Research using transgenic mice showed that while the RNA alone does not cause harm, the presence of FMRpolyG is pathogenic and disrupts the structure of nuclear lamina in neurons derived from FXTAS patient cells.
- - The study found that the protein LAP2β can counteract the neuronal damage caused by FMRpolyG, indicating that changes in nuclear lamina architecture play a significant role in the
Article Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a limited expansion of CGG repeats in the 5' UTR of FMR1. Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters specific proteins, and translation of CGG repeats into a polyglycine-containing protein, FMRpolyG. Here we developed transgenic mice expressing CGG repeat RNA with or without FMRpolyG. Expression of FMRpolyG is pathogenic, while the sole expression of CGG RNA is not. FMRpolyG interacts with the nuclear lamina protein LAP2β and disorganizes the nuclear lamina architecture in neurons differentiated from FXTAS iPS cells. Finally, expression of LAP2β rescues neuronal death induced by FMRpolyG. Overall, these results suggest that translation of expanded CGG repeats into FMRpolyG alters nuclear lamina architecture and drives pathogenesis in FXTAS.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5263258 | PMC |
| http://dx.doi.org/10.1016/j.neuron.2016.12.016 | DOI Listing |
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