Figure 3. RNA-binding proteins (RBPs) are involved in FXTAS pathogenesis.
Three RNA-binding proteins, Pur α, hnRNP A2/B1, and CUGBP1, were found to bind rCGG repeats either directly (Pur α and hnRNP A2/B1) or indirectly (CUGBP1, through the interaction with hnRNP A2/B1). HnRNP A2/B1 forms a complex with CUGBP1 to bind to rCGG repeats, which is independent of Pur α. Overexpression of these proteins can suppress neuronal cell death caused by fragile X premutation rCGG repeats, supporting the model that sequestration of these proteins by the overproduced rCGG repeats in FXTAS prevents them from carrying out their normal functions, leading to abnormal RNA metabolism and neurodegeneration.