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.

Whether elongated CAG repeats act as slippery or stimulatory sequences or both remains to be determined. Nonetheless, the information gathered thus far seems to confirm the role of CAG repeats in generating frameshifted proteins because the frequency of frameshifted events increases with the length of the CAG tract; long CAA repeats that do not form hairpins do not give rise to frameshifted proteins; frameshifting events can occur at every position within the CAG tract; frameshifting is cell-and tissue-type dependent and (v) frameshifted proteins are toxic to cells and affect polyQ aggregation kinetics. It is possible that frameshifting is a more widespread phenomenon and also occurs on the expanded CAG repeats involved in SCA1, 2, 3, 6, 7, 17, DRPLA and SBMA. Experiments with the use of dedicated antibodies (allowing the detection of Ala ((−1) frame) and Ser ((+1) frame)-containing proteins) could clarify this matter.