HUMAN TRA2 PROTEINS ARE SEQUENCE-SPECIFIC ACTIVATORS OF PRE-MESSENGER-RNA SPLICING

The RNA-binding protein Tra2 is an important regulator of sex determin ation in Drosophila. Recently, two mammalian Tra2 homologs of unknown function have been described. Here, we show that human Tra2 proteins a re present in HeLa cell nuclear extracts and that they bind efficientl y and specifically to a previously characterized pre-mRNA splicing enh ancer element. Indeed, both purified proteins bound preferentially to RNA sequences containing GAA repeats, characteristic of many enhancer elements. Neither Tra2 protein functioned in constitutive splicing in vitro, but both activated enhancer-dependent splicing in a sequence-sp ecific manner and restored it after inhibition with competitor RNA. Ou r findings indicate that mammalian Tra2 proteins are sequence-specific splicing activators that likely participate in the control of cell-sp ecific splicing patterns.