title: Upstream Open Reading Frames Differentially Regulate Gene-specific Translation in the Integrated Stress Response.
abstract: Translation regulation largely occurs during initiation, which features ribosome assembly onto mRNAs and selection of the translation start site. Short, upstream ORFs (uORFs) located in the 5'-leader of the mRNA can be selected for translation. Multiple transcripts associated with stress amelioration are preferentially translated through uORF-mediated mechanisms during activation of the integrated stress response (ISR) in which phosphorylation of the α subunit of eIF2 results in a coincident global reduction in translation initiation. This review presents key features of uORFs that serve to optimize translational control that is essential for regulation of cell fate in response to environmental stresses.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5126.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Young
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5126 rwek@iu.edu.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Wek
mesh_terms: D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006801:Humans; D016366:Open Reading Frames / Q000502:physiology*; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger
keywords: eukaryotic translation initiation; stress response; translation; translation control; translation regulation