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.

RAN translation, which occurs across long hairpinforming CAG repeats of ATXN8 and DMPK transcripts, was consistently found in human embryonic kidney (HEK293T) cells and in murine neuroblastoma (N2a) cells (Supplementary Table S1 and Figure S1 ) and was also demonstrated using CAG transcripts in vivo in SCA8 and DM1 human and mouse tissues (Supplementary Table S2 ). This non-AUG translation leads to the expression of atypical homopolymeric proteins in all three reading frames, producing polyGln in the CAG frame, polyserine (polySer) in the AGC frame and polyalanine (polyAla) in the GCA repeat frame. Furthermore, expanded CUG repeats are likely to be RAN translated in three possible frames (the CUG, UGC and GCU frames), coding, respectively, polyleucine (polyLeu), polycysteine (polyCys) and polyAla (14) .