title: A new paradigm for translational control: inhibition via 5'-3' mRNA tethering by Bicoid and the eIF4E cognate 4EHP.
abstract: Translational control is a key genetic regulatory mechanism implicated in regulation of cell and organismal growth and early embryonic development. Initiation at the mRNA 5' cap structure recognition step is frequently targeted by translational control mechanisms. In the Drosophila embryo, cap-dependent translation of the uniformly distributed caudal (cad) mRNA is inhibited in the anterior by Bicoid (Bcd) to create an asymmetric distribution of Cad protein. Here, we show that d4EHP, an eIF4E-related cap binding protein, specifically interacts with Bcd to suppress cad translation. Translational inhibition depends on the Bcd binding region (BBR) present in the cad 3' untranslated region. Thus, simultaneous interactions of d4EHP with the cap structure and of Bcd with BBR renders cad mRNA translationally inactive. This example of cap-dependent translational control that is not mediated by canonical eIF4E defines a new paradigm for translational inhibition involving tethering of the mRNA 5' and 3' ends.
authors.affiliation: Department of Biochemistry, McGill Cancer Center, McGill University, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada.
authors.forename: Park F
authors.initials: PF
authors.lastname: Cho
authors.forename: Francis
authors.initials: F
authors.lastname: Poulin
authors.forename: Yoon Andrew
authors.initials: YA
authors.lastname: Cho-Park
authors.forename: Ian B
authors.initials: IB
authors.lastname: Cho-Park
authors.forename: Jarred D
authors.initials: JD
authors.lastname: Chicoine
authors.forename: Paul
authors.initials: P
authors.lastname: Lasko
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D039381:RNA Cap-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D018398:Homeodomain Proteins; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C056478:bcd protein, Drosophila; C084564:cad protein, Drosophila; C504669:eIF4EHP protein, Drosophila