title: A posttranscriptional mechanism that controls Ptbp1 abundance in the Xenopus epidermis.
abstract: The output of alternative splicing depends on the cooperative or antagonistic activities of several RNA-binding proteins (RBPs), like Ptbp1 and Esrp1 in Xenopus. Fine-tuning of the RBP abundance is therefore of prime importance to achieve tissue- or cell-specific splicing patterns. Here, we addressed the mechanisms leading to the high expression of the ptbp1 gene, which encodes Ptbp1, in Xenopus epidermis. Two splice isoforms of ptbp1 mRNA differ by the presence of an alternative exon 11, and only the isoform including exon 11 can be translated to a full-length protein. In vivo minigene assays revealed that the nonproductive isoform was predominantly produced. Knockdown experiments demonstrated that Esrp1, which is specific to the epidermis, strongly stimulated the expression of ptbp1 by favoring the productive isoform. Consequently, knocking down esrp1 phenocopied ptbp1 inactivation. Conversely, Ptbp1 repressed the expression of its own gene by favoring the nonproductive isoform. Hence, a complex posttranscriptional mechanism controls Ptbp1 abundance in Xenopus epidermis: skipping of exon 11 is the default splicing pattern, but Esrp1 stimulates ptbp1 expression by favoring the inclusion of exon 11 up to a level that is limited by Ptbp1 itself. These results decipher a posttranscriptional mechanism that achieves various abundances of the ubiquitous RBP Ptbp1 in different tissues.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France agnes.mereau@univ-rennes1.fr luc.paillard@univ-rennes1.fr.
authors.forename: Agnès
authors.initials: A
authors.lastname: Méreau
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Anquetil
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lerivray
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Viet
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Schirmer
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Audic
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Legagneux
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Hardy
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement, UMR 6290, Rennes, France Université de Rennes 1, Rennes, France agnes.mereau@univ-rennes1.fr luc.paillard@univ-rennes1.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Paillard
mesh_terms: D017398:Alternative Splicing; D029845:Amphibian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004625:Embryo, Nonmammalian; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism*; D005091:Exons; D005838:Genotype; D007438:Introns; D010641:Phenotype; D038941:Polypyrimidine Tract-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D029845:Amphibian Proteins; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein