Figure 3

Potential mechanisms of FMR1 mRNA toxicity. Although numerous studies point to RNA toxicity as the underlying pathogenic trigger in fragile X-associated tremor ataxia syndrome (FXTAS), the specific mechanism for such toxicity is not known. Possibilities include (1) sequestration of one or more proteins that bind to the RNA, thus attenuating their other cell functions; (2) protein activation upon binding to the CGG-repeat RNA, leading to dysregulation of one or more signaling cascades; and (3) various co-transcriptional process, such as R-loop formation, that lead to DNA damage/repair signaling and consequent cellular dysregulation.