1. The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform
- Author
-
Richard M. Harland, Peter Walentek, and Darwin S. Dichmann
- Subjects
Gene isoform ,RNA Splicing ,Xenopus ,Regulator ,Xenopus Proteins ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Animals, Genetically Modified ,Xenopus laevis ,03 medical and health sciences ,0302 clinical medicine ,Somitogenesis ,Medicine and Health Sciences ,Animals ,Protein Isoforms ,lcsh:QH301-705.5 ,030304 developmental biology ,Genetics ,0303 health sciences ,Alternative splicing ,Intron ,Morphant ,Harland [BRII recipient] ,Exon skipping ,Wnt Proteins ,Alternative Splicing ,lcsh:Biology (General) ,Somites ,RNA splicing ,030217 neurology & neurosurgery - Abstract
SummaryAlternative 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.
- Published
- 2015
- Full Text
- View/download PDF