RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders

Wojciechowska, Marzena; Olejniczak, Marta; Galka-Marciniak, Paulina; Jazurek, Magdalena; Krzyzosiak, Wlodzimierz J.

Another explanation of frameshifting might rely on ribosomal slippage and the occurrence of slippery sequences within ATXN3 and HTT transcripts ( Figure 3 ) (103) . However, as frameshifting occurs stochastically at any CAG codon within the repeat stretch, as demonstrated in HD (30) , it seems unlikely that slippery sequences proceeding a repeat tract play a mechanistic role as a trigger of changes in reading frames. Is it possible that CAG repeats themselves act as unusual slippery sequences? Viral slippery sequences composed of the heptameric motif N NNW WWH (IUPAC) enable repairing of the nonwobble bases of both the aa-tRNAs and peptidyl-tRNAs with the (−1) codons (104) . In light of this fact, it remains a mystery what factors would help to maintain interactions between the frameshifted 5 GCA3 codon and the 5 CUG3 anticodon, where no Watson-Crick pairs would be possible (Figure 4 ) (103) .