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XB-ART-50079
Cell Rep. February 3, 2015; 10 (4): 527-36.

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.

PubMed ID: 25620705
PMC ID: PMC4351874
Article link: Cell Rep.
Grant support: R01 GM042341 NIGMS NIH HHS , R01 GM086321 NIGMS NIH HHS , GM086321 NIGMS NIH HHS , GM42341 NIGMS NIH HHS , R01 GM042341 NIGMS NIH HHS , R01 GM086321 NIGMS NIH HHS , GM086321 NIGMS NIH HHS , GM42341 NIGMS NIH HHS , R01 GM042341 NIGMS NIH HHS , R01 GM086321 NIGMS NIH HHS , GM086321 NIGMS NIH HHS , GM42341 NIGMS NIH HHS

Genes referenced: aasdh acta2 actn3 alms1 atp1a1 cav1 cdc34 cep104 chrng ctnnd2 ctrl dip2b ero1a fam169a gata4 gata6 hey1 mdm1 mybph myh1 myh2 myh4 myh9 myod1 nxpe2 odc1 pcdh8 pcdh8.2 ppil3 qser1 scel scn3b scn5a sema4b sox17a stxbp2 tnnt3 tra2b wnt11 wnt11b zfand1 t

Morpholinos referenced: tra2b MO1 tra2b MO2 wnt11b MO3

References:
Afouda, 2008, Pubmed, Xenbase[+]


Article Images: [+] show captions

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