Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer

Alternative mRNA splicing of the fibronectin EDI exon is controlled by a pu rine-rich exonic splicing enhancer (ESE), postulated as a binding site for SR proteins. By using a transient expression alternative splicing assay com bined with promoter swapping, we have demonstrated that the promoter can al so control EDI splicing, arguing for coupling between the transcription and splicing machineries. We now report that the SR proteins SF2/ASF and 9G8 s timulate EDI splicing in vivo and that their effect requires an intact EDI ESE. Most importantly, we show that sensitivity to these SR proteins critic ally depends on the promoter structure, suggesting that the transcription m achinery modulates their recruitment to the ESE.