title: Transcriptome-wide modulation of splicing by the  exon junction complex.
abstract: BACKGROUND
  The exon junction complex (EJC) is a dynamic multi-protein complex deposited onto nuclear spliced mRNAs upstream of exon-exon junctions. The four core proteins, eIF4A3, Magoh, Y14 and MLN51, are stably bound to mRNAs during their lifecycle, serving as a binding platform for other nuclear and cytoplasmic proteins. Recent evidence has shown that the EJC is involved in the splicing regulation of some specific events in both Drosophila and mammalian cells.
  
  
  RESULTS
  Here, we show that knockdown of EJC core proteins causes widespread alternative splicing changes in mammalian cells. These splicing changes are specific to EJC core proteins, as knockdown of eIF4A3, Y14 and MLN51 shows similar splicing changes, and are different from knockdown of other splicing factors. The splicing changes can be rescued by a siRNA-resistant form of eIF4A3, indicating an involvement of EJC core proteins in regulating alternative splicing. Finally, we find that the splicing changes are linked with RNA polymerase II elongation rates.
  
  
  CONCLUSIONS
  Taken together, this study reveals that the coupling between EJC proteins and splicing is broader than previously suspected, and that a possible link exists between mRNP assembly and splice site recognition.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Valentine
authors.initials: V
authors.lastname: Murigneux
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Hir
mesh_terms: D019295:Computational Biology / Q000379:methods; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007365:Intercellular Junctions; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: C459802:CASC3 protein, human; C491494:MAGOH protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C406243:RBM8A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D039601:Eukaryotic Initiation Factor-4A; D012319:RNA Polymerase II; C403493:EIF4A3 protein, human; D053487:DEAD-box RNA Helicases