Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation

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Bressler, Kamiko R.
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
Cap-dependent translation drives the global synthesis of proteins. Under stress conditions global protein production is attenuated, yet the translation of ATF4 is upregulated through uORF- mediated translation initiation. eIF5B has been shown to deliver initiator-tRNA during non-canonical translation initiation. As such, we defined the role of eIF5B in the non-canonical translation of ATF4, and p27. Through polysome profiling and luciferase reporter assays, we confirmed that eIF5B facilitates uORF2-mediated repression of ATF4 translation. We determined that eIF5B has transcriptome-wide effects on signaling pathways, verifying activation of the JNK arm of the MAPK pathway and upregulation of dyskerin. I investigated the role eIF5B has in regulation of p27, and suggest that the mechanism is IRES-dependent. This study furthers the understanding into mechanisms of alternative translation initiation, which is critical to gene expression regulation.
Messenger RNA , Proteins--Synthesis , Ribosomes