THE MAMMALIAN HOMOLOG OF SUPPRESSOR-OF-WHITE-APRICOT REGULATES ALTERNATIVE MESSENGER-RNA SPLICING OF CD45 EXON-4 AND FIBRONECTIN IIICS

We have previously described human (HsSWAP) and mouse (MmSWAP) homolog s to the Drosophila alternative splicing regulator suppressor-of-white -apricot (su(w(a)) or DmSWAP), DmSWAP was formally defined as an alter native splicing regulator by studies showing that it autoregulates spl icing of its own pre-mRNA. We report here that mammalian SWAP regulate s its own splicing, and also the splicing of fibronectin and CD45. Usi ng an in vivo system of cell transfection, mammalian SWAP regulated 5' splice site selection in splicing of its own second intron, SWAP enha nced splicing to the distal 5' splice site, whereas the SR protein ASF /SF2 enhanced splicing to the proximal site, SWAP also regulated alter native splicing of the fibronectin IIICS region by promoting exclusion of the entire IIICS region, In contrast, ASF/SF2 stimulated inclusion of the entire IIICS region. Finally, SWAP regulated splicing of CD45 exon 4, promoting exclusion of this exon, an effect also seen with ASF /SF2, Experiments using SWAP deletion mutants showed that splicing reg ulation of the fibronectin IIICS region and CD45 exon 4 requires a reg ion including a carboxyl-terminal arginine/serine (WS)-rich motif, Sin ce WS motifs of various splicing proteins have been shown to interact with each other, these results suggest that the WS motif in SWAP may r egulate splicing, at least in part, through interactions with other R/ S containing splicing factors.