The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform
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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714010997 |
| _version_ | 1818550544014245888 |
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| author | Darwin S. Dichmann Peter Walentek Richard M. Harland |
| author_facet | Darwin S. Dichmann Peter Walentek Richard M. Harland |
| author_sort | Darwin S. Dichmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:47:52Z |
| format | Article |
| id | doaj.art-4e917aed01e146c7bb3430b8cc021523 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T08:47:52Z |
| publishDate | 2015-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4e917aed01e146c7bb3430b8cc0215232022-12-22T00:30:23ZengElsevierCell Reports2211-12472015-02-0110452753610.1016/j.celrep.2014.12.046The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b IsoformDarwin S. Dichmann0Peter Walentek1Richard M. Harland2Department of Molecular & Cell Biology, 142 Life Sciences Addition #3200, University of California, Berkeley, Berkeley, CA 94720-3200, USADepartment of Molecular & Cell Biology, 142 Life Sciences Addition #3200, University of California, Berkeley, Berkeley, CA 94720-3200, USADepartment of Molecular & Cell Biology, 142 Life Sciences Addition #3200, University of California, Berkeley, Berkeley, CA 94720-3200, USAAlternative 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.http://www.sciencedirect.com/science/article/pii/S2211124714010997 |
| spellingShingle | Darwin S. Dichmann Peter Walentek Richard M. Harland The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform Cell Reports |
| title | The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform |
| title_full | The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform |
| title_fullStr | The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform |
| title_full_unstemmed | The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform |
| title_short | The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform |
| title_sort | alternative splicing regulator tra2b is required for somitogenesis and regulates splicing of an inhibitory wnt11b isoform |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714010997 |
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