title: Coupling 40S ribosome recruitment to modification of a cap-binding initiation factor by eIF3 subunit e.
abstract: 40S ribosomes are loaded onto capped mRNAs via the multisubunit translation initiation factors eIF3 and eIF4F. While eIF4E is the eIF4F cap recognition component, the eIF4G subunit associates with 40S-bound eIF3. How this intricate process is coordinated remains poorly understood. Here, we identify an eIF3 subunit that regulates eIF4F modification and show that eIF3e is required for inducible eIF4E phosphorylation. Significantly, recruitment of the eIF4E kinase Mnk1 (MAPK signal-integrating kinase 1) to eIF4F depended on eIF3e, and eIF3e was sufficient to promote Mnk1-binding to eIF4G. This establishes a mechanism by which 40S ribosome loading imparts a phosphorylation mark on the cap-binding eIF4F complex that regulates selective mRNA translation and is synchronized by a specific eIF3 subunit.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Walsh
authors.forename: Ian
authors.initials: I
authors.lastname: Mohr
mesh_terms: D002845:Chromatography; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport; D039381:RNA Cap-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D039621:Eukaryotic Initiation Factor-3; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits; D039381:RNA Cap-Binding Proteins; C491395:MKNK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Mnk1; eIF3; eIF4E phosphorylation; ribosome recruitment; translation initiation
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