The atypical RNA-binding protein TAF15 regulates dorsoanterior neural development through diverse mechanisms in Xenopus tropicalis.

The FET family of atypical RNA-binding proteins includes Fused in sarcoma (Fus), Ewings sarcoma (EWS), and the TATA-binding protein-associate factor 15 (TAF15). All FET family members are highly conserved from fish to mammals, suggesting an independent and specialized requirement for each protein. Fus is necessary for the proper splicing of genes required for mesoderm differentiation and cell adhesion in Xenopus, but the role, if any, that EWS and TAF15 play in development remains unknown. Here we define the role maternally deposited and zygotically transcribed TAF15 plays in development. We find that TAF15 is essential for the proper development of dorsoanterial neural tissues, and by sequencing the RNA from single TAF15-depleted embryos and measuring changes in transcript abundance and exon usage we found TAF15 regulates dorsoanterior neural tissue development through regulating fgfr4 and ventx2.1. Intriguingly, we find that TAF15 uses two distinct mechanisms to downregulate FGFR4 expression: 1) retention of a single intron within fgfr4 and 2) reduction of total fgfr4 transcript. Intron retention was identified when both maternal and zygotic TAF15 is depleted, while depletion of zygotic TAF15 alone leads to regulation of fgfr4 total transcripts. In this study we find that TAF15 plays an integral and pleiotropic role in the development of dorsoanterior neural tissues and further identify two novel mechanisms of gene regulation by TAF15, suggesting TAF15 gene regulation is target and cofactor-dependent, subject to the milieu of factors that are present at different times of development.