title: eIF3 targets cell-proliferation messenger RNAs for translational activation or repression.
abstract: Regulation of protein synthesis is fundamental for all aspects of eukaryotic biology by controlling development, homeostasis and stress responses. The 13-subunit, 800-kilodalton eukaryotic initiation factor 3 (eIF3) organizes initiation factor and ribosome interactions required for productive translation. However, current understanding of eIF3 function does not explain genetic evidence correlating eIF3 deregulation with tissue-specific cancers and developmental defects. Here we report the genome-wide discovery of human transcripts that interact with eIF3 using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific program of messenger RNAs involved in cell growth control processes, including cell cycling, differentiation and apoptosis, via the mRNA 5' untranslated region. Surprisingly, functional analysis of the interaction between eIF3 and two mRNAs encoding the cell proliferation regulators c-JUN and BTG1 reveals that eIF3 uses different modes of RNA stem-loop binding to exert either translational activation or repression. Our findings illuminate a new role for eIF3 in governing a specialized repertoire of gene expression and suggest that binding of eIF3 to specific mRNAs could be targeted to control carcinogenesis.
authors: 1] Department of Molecular &Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Center for RNA Systems Biology, University of California, Berkeley, Berkeley, California 94720, USA.
authors: Amy S Y
authors: AS
authors: Lee
authors: 1] Department of Molecular &Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Howard Hughes Medical Institute (HHMI), University of California, Berkeley, Berkeley, California 94720, USA.
authors: Philip J
authors: PJ
authors: Kranzusch
authors: 1] Department of Molecular &Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Center for RNA Systems Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA [4] Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors: Jamie H D
authors: JH
authors: Cate
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D017209:Apoptosis; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D003432:Cross-Linking Reagents; D015536:Down-Regulation; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D010442:Peptide Chain Initiation, Translational; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D012263:Ribonucleosides; D012270:Ribosomes / Q000378:metabolism; D013379:Substrate Specificity; D059467:Transcriptome
chemical_list: D020121:5' Untranslated Regions; D003432:Cross-Linking Reagents; D039621:Eukaryotic Initiation Factor-3; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012263:Ribonucleosides; C074086:BTG1 protein, human