title: EJC core component MLN51 interacts with eIF3 and activates translation.
abstract: The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonucleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8197, 75230 Paris Cedex 05, France.
authors.forename: Pierre-Etienne
authors.initials: PE
authors.lastname: Chazal
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Daguenet
authors.forename: Corinne
authors.initials: C
authors.lastname: Wendling
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ulryck
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomasetto
authors.forename: Bruno
authors.initials: B
authors.lastname: Sargueil
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Hir
mesh_terms: D001692:Biological Transport; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007438:Introns; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: C459802:CASC3 protein, human; D039621:Eukaryotic Initiation Factor-3; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein