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Genes Dev 2012 Jun 15;2612:1351-63. doi: 10.1101/gad.187278.112.
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fus/TLS orchestrates splicing of developmental regulators during gastrulation.

Here we investigated the function of the atypical RNA-binding protein fus/TLS (fused in sarcoma/translocated in sarcoma) during early frog development. We found that fus is necessary for proper mRNA splicing of a set of developmental regulatory genes during early frog development and gastrulation. Upon fus knockdown, embryos fail to gastrulate and show mesodermal differentiation defects that we connect to intron retention in fgf8 (fibroblast growth factor 8) and fgfr2 (fgf receptor 2) transcripts. During gastrulation, the animal and marginal regions dissociate, and we show that this is caused, at least in part, by intron retention in cdh1 transcripts. We confirm the specificity of splicing defects at a genomic level using analysis of RNA sequencing (RNA-seq) and show that 3%-5% of all transcripts display intron retention throughout the pre-mRNA. By analyzing gene ontology slim annotations, we show that the affected genes are enriched for developmental regulators and therefore represent a biologically coherent set of targets for fus regulation in embryogenesis. This shows that fus is central to embryogenesis and may provide information on its function in neurodegenerative disease.

PubMed ID: 22713872
PMC ID: PMC3387662
Article link: Genes Dev
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acvr1b adamts1 adap1l admp admp2 ag1 aggf1 alcam aldh1a2 alpl amotl2 api5 arid4a arl4a arl5c armc7 arnt arrdc2 asb7 asxl1 atf3 atg16l1 atp12a atp1b1 atp1b2 avp azin2 bambi bcor bend3 bix1.1 bix1.2 bmp2 bmp4 bmp7.2 bmpr1a brd2 btbd10 btg5.2 camlg cass4 cd81 cdc14b cdc16 cdc25b cdc42ep4 cdca3 cdca4 cdca5 cdca7 cdh1 cdkn2aip cdx1 cdx2 cdx4 celsr1 cenpf cep19 chrd ciz1 clk1 clk2 clk3 creb3l2 cxcr4 eomes fgf8 fgfr2 fus hpdl mt-tr notch1 nt5c3a odc1 palm2akap2 pfkfb3 shh sox17b.1 tbxt tfap2a trna
Morpholinos: fus MO1 fus MO2 fus MO3 fus MO4 fus MO5

Phenotypes: Xla Wt + fus MO (fig.1.h) [+]

Article Images: [+] show captions
References [+] :
Blunt, Overlapping expression and redundant activation of mesenchymal fibroblast growth factor (FGF) receptors by alternatively spliced FGF-8 ligands. 1997, Pubmed