Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism

Autor: Chelsea Moore, Madelyn Hilgers, Ariana Cecil, Naoki Tani, Akira Nakamura, Katsura Asano, Ye Zou, Rahul Jaiswal, Peter K. Todd, Chingakham Ranjit Singh, Masayo Asano, Sarah Gillaspie, Eric Aube, Izumi Asano, Mackenzie M. Thornton, Azuma Takasu, M. Rebecca Glineburg, Carlos R. Escalante
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Models
Molecular
Ataxia
QH301-705.5
Protein subunit
Eukaryotic Initiation Factor-3
Eukaryotic Initiation Factor-2
Codon
Initiator
non-AUG start codon
Small ribosomal subunit
Neuronal toxicity
Ribosome
Models
Biological
translation initiation
General Biochemistry
Genetics and Molecular Biology
Article
Eukaryotic translation
Protein Domains
RAN translation
medicine
Animals
Drosophila Proteins
Humans
cancer
Receptors
Immunologic
Biology (General)
Peptide Chain Initiation
Translational
Adaptor Proteins
Signal Transducing
Regulation of gene expression
Mechanism (biology)
Chemistry
Neurodegeneration
Translation (biology)
medicine.disease
Antigens
Differentiation
Cell biology
DNA-Binding Proteins
HEK293 Cells
ribosome
Protein Biosynthesis
Transcription preinitiation complex
Mutation
Ran
Drosophila
FXTAS
medicine.symptom
Trinucleotide Repeat Expansion
Protein Binding
Zdroj: Cell Reports, Vol 36, Iss 2, Pp 109376-(2021)
Cell Rep
ISSN: 2211-1247
Popis: Summary: 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.
Databáze: OpenAIRE
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