Singh, C.R., Glineburg, M.R., Moore, C., Tani, N., Jaiswal, R., Zou, Y., Aube, E., Gillaspie, S., Thornton, M., Cecil, A., Hilgers, M., Takasu, A., Asano, I., Asano, M., Escalante, C.R., Nakamura, A., Todd, P.K., Asano, K. (2021). Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism.  Cell Rep. 36(2): 109376.

FBrf0249503

Research paper

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. In Drosophila, 5MP/Kra represses neuronal toxicity and enhances the lifespan in an FXTAS disease model. These results implicate 5MP in protecting cells from unwanted byproducts of non-AUG translation in neurodegeneration.

PMC8363759 (PMC) (EuropePMC)