FUNCTIONAL ASSOCIATION BETWEEN PROMOTER STRUCTURE AND TRANSCRIPT ALTERNATIVE SPLICING

It has been assumed that constitutive and regulated splicing of RNA po lymerase II transcripts depends exclusively on signals present in the RNA molecule. Here we show that changes in promoter structure strongly affect splice site selection. We investigated the splicing of the ED I exon, which encodes a facultative type III repeat of fibronectin, wh ose inclusion is regulated during development and in proliferative pro cesses. We used an alternative splicing assay combined with promoter s wapping to demonstrate that the extent of ED I splicing is dependent o n the promoter structure from which the transcript originated and that this regulation is independent of the promoter strength. Thus, these results provide the first evidence for coupling between alternative sp licing and promoter-specific transcription, which agrees with recent c ytological and biochemical evidence of coordination between splicing a nd transcription.