ReviewRNA-mediated neurodegeneration in fragile X-associated tremor/ataxia syndrome

Carriers of fragile X syndrome (FXS) have FMR1 alleles, called premutations, with a number of 5′-untranslated-CGG repeats somewhere between patients, who have over 200 repeats, and normal individuals, with fewer than 60 repeats. Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has been recognized in older male fragile X premutation carriers, and FXTAS is uncoupled from the neurodevelopmental disorder, FXS. Several lines of evidence have led to the proposal of an RNA (fragile X premutation rCGG repeat)-mediated gain-of-function toxicity model for FXTAS, in which rCGG repeat-binding proteins (RBPs) could become functionally limited by their sequestration to lengthy rCGG repeats. In this review, we will discuss the recent progress towards understanding the molecular basis of RNA-mediated neurodegeneration in FXTAS.This article is part of a Special Issue entitled: RNA-Binding Proteins

► FXTAS is a neurodegenerative disorder specifically associated with fragile X premutation carriers. ► Recent works suggest that FXTAS is caused by fragile X rCGG repeat. ► Molecular pathogenesis of FXTAS is discussed. ► Development of potential therapeutic intervention for FXTAS is discussed.