title: Robust identification of Ptbp1-dependent splicing events by a junction-centric approach in Xenopus laevis.
abstract: Regulation of alternative splicing is an important process for cell differentiation and development. Down-regulation of Ptbp1, a regulatory RNA-binding protein, leads to developmental skin defects in Xenopus laevis. To identify Ptbp1-dependent splicing events potentially related to the phenotype, we conducted RNAseq experiments following Ptbp1 depletion. We systematically compared exon-centric and junction-centric approaches to detect differential splicing events. We showed that the junction-centric approach performs far better than the exon-centric approach in Xenopus laevis. We carried out the same comparisons using simulated data in human, which led us to propose that the better performances of the junction-centric approach in Xenopus laevis essentially relies on an incomplete exonic annotation associated with a correct transcription unit annotation. We assessed the capacity of the exon-centric and junction-centric approaches to retrieve known and to discover new Ptbp1-dependent splicing events. Notably, the junction-centric approach identified Ptbp1-controlled exons in agfg1, itga6, actn4, and tpm4 mRNAs, which were independently confirmed. We conclude that the junction-centric approach allows for a more complete and informative description of splicing events, and we propose that this finding might hold true for other species with incomplete annotations.
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Noiret
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Méreau
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Angrand
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Bervas
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Gautier-Courteille
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Legagneux
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Deschamps
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lerivray
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Viet
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Hardy
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Paillard
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne, Biosit, Rennes 35000, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, Rennes 35000, France. Electronic address: yann.audic@univ-rennes1.fr.
authors.forename: Yann
authors.initials: Y
authors.lastname: Audic
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D003198:Computer Simulation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005091:Exons / Q000235:genetics; D015723:Gene Library; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology*; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D060172:Morpholinos / Q000494:pharmacology; D038941:Polypyrimidine Tract-Binding Protein / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D060172:Morpholinos; D012333:RNA, Messenger; D029867:Xenopus Proteins; C000608280:polypyrimidine tract binding protein 1, Xenopus; D038941:Polypyrimidine Tract-Binding Protein
keywords: Allotetraploid; DEXSeq; Differential splicing; Genome wide; Skin defects