Cutting edge Seminar

※  Zoom online/ Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle

 

Speaker: Katsura Asano (Professor, Division of Biology, Kansas State University)

Title: Human oncoprotein 5MP1 suppresses general and repeat-associated non-AUG translation by a common mechanism through eIF3 c-subunit

 

Date&Time: 26 Aug.  (Wed.) 2020, 12:00- 13:00

Venue:  Zoom online/ Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle

 

Abstract:

eIF5-mimic protein 1 (5MP1) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. It is frequently amplified in various types of cancer. In colorectal cancer, 5MP overexpression reprograms translation of the oncogenic transcription factor, c-Myc, by repressing its less oncogenic CUG-initiated isoform, consequently promoting translation from the shorter, more oncogenic AUG-initiated isoform. 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, 5MP1 assures stoichiometric and ordered interaction of eIF3c within the PIC, thereby increasing the accuracy of initiation. A mutation that inhibits 5MP1 binding to eIF3c causes eIF3c to recruit an additional copy of eIF5, thereby enhancing eIF2 GTP hydrolysis, and reducing codon fidelity, leading to increased translation initiation at non-AUG codons. In Drosophila, 5MP/Kra can also repress neuronal toxicity induced by the RAN product FMRpolyG, and enhance lifespan in flies expressing FmrpolyG. These results indicate a role for 5MP in protecting cells from unwanted byproducts of non-AUG translation in neural development and likely in carcinogenesis.