title: Exon Junction Complexes Show a Distributional Bias toward Alternatively Spliced mRNAs and against mRNAs Coding for Ribosomal Proteins.
abstract: The exon junction complex (EJC) connects spliced mRNAs to posttranscriptional processes including RNA localization, transport, and regulated degradation. Here, we provide a comprehensive analysis of bona fide EJC binding sites across the transcriptome including all four RNA binding EJC components eIF4A3, BTZ, UPF3B, and RNPS1. Integration of these data sets permits definition of high-confidence EJC deposition sites as well as assessment of whether EJC heterogeneity drives alternative nonsense-mediated mRNA decay pathways. Notably, BTZ (MLN51 or CASC3) emerges as the EJC subunit that is almost exclusively bound to sites 20-24 nucleotides upstream of exon-exon junctions, hence defining EJC positions. By contrast, eIF4A3, UPF3B, and RNPS1 display additional RNA binding sites suggesting accompanying non-EJC functions. Finally, our data show that EJCs are largely distributed across spliced RNAs in an orthodox fashion, with two notable exceptions: an EJC deposition bias in favor of alternatively spliced transcripts and against the mRNAs that encode ribosomal proteins.
authors.affiliation: Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Im Neuenheimer Feld 350, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hauer
authors.affiliation: Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Sieber
authors.affiliation: European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarzl
authors.affiliation: Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Im Neuenheimer Feld 350, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Hollerer
authors.affiliation: European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Faculty of Computer and Information Science, University of Ljubljana, Vecna Pot 113, 1000 Ljubljana, Slovenia.
authors.forename: Tomaz
authors.initials: T
authors.lastname: Curk
authors.affiliation: European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Alleaume
authors.affiliation: Molecular Medicine Partnership Unit (MMPU), Im Neuenheimer Feld 350, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: hentze@embl.de.
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
authors.affiliation: Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Im Neuenheimer Feld 350, 69120 Heidelberg, Germany. Electronic address: andreas.kulozik@med.uni-heidelberg.de.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D006801:Humans; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D012269:Ribosomal Proteins