All vertebrates possess lymphocytes, enabling the functional interrogation of this evolutionarily conserved organizing principle of adaptive immunity in non-mammalian species. A forward genetic screen in zebrafish indicated that a mutation of tnpo3, encoding a regulator of alternative splicing of pre-mRNAs, specifically impaired intrathymic T cell development. In mouse T cells, Tnpo3 deficiency predominantly disrupted the splicing of genes encoding RNA-binding motifs, and it specifically blocked the splicing of Va11, associated with reduced numbers of peripheral T cells and the complete loss of iNKT cells. Our results reveal an evolutionarily conserved function of a pre-mRNA processing factor for T cell development, uncovering a previously unappreciated checkpoint during the formation of mature mRNAs of the Tcra gene. SOURCE: Andreas,S.,Richter Max Planck Institute of Immunobiology and Epigenetics

Pluto Bioinformatics

GSE77137: An evolutionarily conserved function of the pre-mRNA splicing regulator TNPO3 for T cell development