title: The Ski2-family helicase Obelus regulates Crumbs alternative splicing and cell polarity.
abstract: Alternative splicing can have profound consequences for protein activity, but the functions of most alternative splicing regulators are not known. We show that Obelus, a conserved Ski2-family helicase, is required for cell polarity and adherens junction organization in the Drosophila melanogaster embryo. In obelus mutants, epithelial cells display an expanded apical domain, aggregation of adherens junctions at the cell membrane, and microtubule-dependent defects in centrosome positioning. Through whole-genome transcriptome analysis, we found that Obelus is required for the alternative splicing of a small number of transcripts in the early embryo, including the pre-mRNA that encodes the apical polarity protein Crumbs. In obelus mutants, inclusion of an alternative exon results in increased expression of a Crumbs isoform that contains an additional epidermal growth factor-like repeat in the extracellular domain. Overexpression of this alternative Crumbs isoform recapitulates the junctional aggregation and centrosome positioning defects of obelus mutants. These results indicate that regulation of Crumbs alternative splicing by the Obelus helicase modulates epithelial polarity during development.
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065 Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
authors.forename: Athea
authors.initials: A
authors.lastname: Vichas
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065 Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Laurie
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065 Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065 zallenj@mskcc.org.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Zallen
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D030801:Animals, Genetically Modified; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D020365:RNA Helicases / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; C064360:crb protein, Drosophila; D020365:RNA Helicases; C000606333:obe protein, Drosophila