title: The alternative splicing regulator Tra2b is required for somitogenesis and regulates splicing of an inhibitory Wnt11b isoform.
abstract: Alternative splicing is pervasive in vertebrates, yet little is known about most isoforms or their regulation. transformer-2b (tra2b) encodes a splicing regulator whose endogenous function is poorly understood. Tra2b knockdown in Xenopus results in embryos with multiple defects, including defective somitogenesis. Using RNA sequencing, we identify 142 splice changes (mostly intron retention and exon skipping), 89% of which are not in current annotations. A previously undescribed isoform of wnt11b retains the last intron, resulting in a truncated ligand (Wnt11b-short). We show that this isoform acts as a dominant-negative ligand in cardiac gene induction and pronephric tubule formation. To determine the contribution of Wnt11b-short to the tra2b phenotype, we induce retention of intron 4 in wnt11b, which recapitulates the failure to form somites but not other tra2b morphant defects. This alternative splicing of a Wnt ligand adds intricacy to a complex signaling pathway and highlights intron retention as a regulatory mechanism.
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition #3200, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: dichmann@berkeley.edu.
authors.forename: Darwin S
authors.initials: DS
authors.lastname: Dichmann
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition #3200, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Walentek
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition #3200, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: harland@berkeley.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Harland
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology*; D019170:Somites / Q000166:cytology* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D020033:Protein Isoforms; D051153:Wnt Proteins; D029867:Xenopus Proteins