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.

Finally, it is yet to be determined whether RAN translation is a unique phenomenon or noncanonical translation that gives rise to novel polypeptides and short proteins is more frequent in cells. Recent studies demonstrate that the human proteome contains a multitude of short ORFencoded peptides (SEPs), which share certain similarities with RAN-translated proteins (111, 112) . Certain SEPs have a regulatory function and affect protein expression by controlling translation re-initiation at downstream initiation codons and by activating the nonsense-mediated mRNA decay pathway (113) . On the other hand, various cryptic peptides, products of alternative translation initiation, act as alternative sources of antigens for major histocompatibility complex class I components (114, 115) . Whether such functions could be performed by RAN translation and frameshifting products is another issue to be addressed.