The Ski2-family helicase Obelus regulates Crumbs alternative splicing and cell polarity
The Ski2-family helicase Obelus regulates Crumbs alternative splicing and cell polarity
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.
- Howard Hughes Medical Institute United States
- Memorial Sloan Kettering Cancer Center United States
Centrosome, Male, Cell Membrane, Cell Polarity, Gene Expression Regulation, Developmental, Membrane Proteins, Epithelial Cells, Adherens Junctions, Microtubules, Animals, Genetically Modified, Alternative Splicing, Drosophila melanogaster, Mutation, RNA Precursors, Animals, Drosophila Proteins, Female, RNA, Messenger, Research Articles, RNA Helicases
Centrosome, Male, Cell Membrane, Cell Polarity, Gene Expression Regulation, Developmental, Membrane Proteins, Epithelial Cells, Adherens Junctions, Microtubules, Animals, Genetically Modified, Alternative Splicing, Drosophila melanogaster, Mutation, RNA Precursors, Animals, Drosophila Proteins, Female, RNA, Messenger, Research Articles, RNA Helicases
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