Unknown

Dataset Information

0

Translation of Expanded CGG Repeats into FMRpolyG Is Pathogenic and May Contribute to Fragile X Tremor Ataxia Syndrome.

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 LAP2? and disorganizes the nuclear lamina architecture in neurons differentiated from FXTAS iPS cells. Finally, expression of LAP2? 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.

SUBMITTER: Sellier C 

PROVIDER: S-EPMC5263258 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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 R  ...[more]

Similar Datasets

Unknown CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome.
| S-EPMC3831531 | biostudies-literature
Unknown Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome.
| S-EPMC3639429 | biostudies-literature
Unknown RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome.
| S-EPMC4492395 | biostudies-literature
Unknown CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome.
| S-EPMC7806243 | biostudies-literature
Unknown Crystal structures of CGG RNA repeats with implications for fragile X-associated tremor ataxia syndrome.
| S-EPMC3167596 | biostudies-literature
Unknown CGG repeats in RNA modulate expression of TDP-43 in mouse and fly models of fragile X tremor ataxia syndrome.
| S-EPMC4204772 | biostudies-literature
Unknown Neuropathology of RAN translation proteins in fragile X-associated tremor/ataxia syndrome.
| S-EPMC6821001 | biostudies-literature
Unknown A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis.
| S-EPMC7668390 | biostudies-literature
Unknown A small molecule that targets r(CGG)(exp) and improves defects in fragile X-associated tremor ataxia syndrome.
| S-EPMC3477254 | biostudies-literature
Unknown Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome.
| S-EPMC3000359 | biostudies-literature