Figure 2
From: Mouse models of the fragile X premutation and fragile X-associated tremor/ataxia syndrome
Potential mechanisms of CGG-repeat RNA toxicity in FMP carriers. (A) Protein sequestration model: RNA binding proteins are sequestered through their interactions with the expanded CGG-repeat RNA. These proteins can in turn recruit other proteins. The net result of sequestration of these proteins is that they are unavailable to carry out their normal functions and critical cellular processes are thereby altered or blocked. (? -Sequestration of SAM68 by CGG expanded repeats is indirect, presumably through protein-protein interactions). (B) Toxic polypeptide model: The 43S translation initiation complex stalls near the CGG repeat hairpin formed on the FMR1 RNA. This promotes the repeat-associated non-AUG translation of FMR1 mRNA using a near-AUG start site. This results in a frame shift and the production of polyglycine- and/or polyalanine-containing polypeptides that somehow interfere with normal cell function or may be directly toxic. FMRP, FMRP, fragile X mental retardation protein; ORF, open reading frame; polyA, polyalanine; polyG, polyglycine.