Document Type
Article
Publication Date
2-14-2018
Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5′UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript. Here we focus on two proposed disease mechanisms for FXTAS: 1) RNA gain-of-function, whereby the mutant RNAs bind specific proteins and preclude their normal functions, and 2) repeat-associated non-AUG (RAN) translation, whereby translation through the CGG or CCG repeats leads to the production of toxic homopolypeptides, which in turn interfere with a variety of cellular functions. Here, we analyze the data generated to date on both of these potential molecular mechanisms and lay out a path forward for determining which factors drive FXTAS pathogenicity.
Recommended Citation
M. Rebecca Glineburg, Peter K. Todd, Nicolas Charlet-Berguerand, Chantal Sellier, “Repeat-associated non-AUG (RAN) translation and other molecular mechanisms in Fragile X Tremor Ataxia Syndrome,” Brain Res., 2018;1693(A):43-54. https://doi.org/10.1016/j.brainres.2018.02.006
Copyright
Elsevier
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Genetics Commons, Nervous System Diseases Commons, Neurosciences Commons, Other Genetics and Genomics Commons
Comments
This article was originally published in Brain Research, volume 1693, part A, in 2018. https://doi.org/10.1016/j.brainres.2018.02.006