Neurodegenerative diseases such as Altzheimer's disease is caused by accumulation of aberrant deleterious peptide products. Repeat-associated non-AUG (RAN) translation is one such mechanism to generate these deleterious peptides. Here we show that a novel translational regulatory protein, 5MP, suppresses RAN translation and thereby inhibits the production of toxic peptides. In collaboration with Peter Todd lab in University of Michigan we used a fly disease model to demonstrate this. Other collaborators are Dr. Carlos Escalante in Virginia Commonwealth University and Dr. Akira Nakamura in Kumamoto University.
Authors: Chingakham Ranjit Singh, Marry Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter Todd, and Katsura Asano
Title: Human oncoprotein 5MP1 suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism.
Journal: Cell Reports, 36, 109376 (2021)