ELEMENTS REGULATING AN ALTERNATIVELY SPLICED EXON OF THE RAT FIBRONECTIN GENE

We have investigated the regulation of splicing of one of the alternat ively spliced exons in the rat fibronectin gene, the EIIIB exon. This 273-nucleotide exon is excluded by some cells and included to various degrees by others. We find that EIIIB is intrinsically poorly spliced and that both its exon sequences and its splice sites contribute to it s poor recognition. Therefore, cells which recognize the EIIIB exon mu st have mechanisms for improving its splicing. Furthermore, in order f or EIIIB to be regulated, a balance must exist between the EIIIB splic e sites and those of its flanking exons. Although the intron upstream of EIIIB does not appear to play a role in the recognition of EIIIB fo r splicing, the intron downstream contains sequence elements which can promote EIIIB recognition in a cell-type-specific fashion. These elem ents are located an unusually long distance from the exon that they re gulate, more than 518 nucleotides downstream from EIIIB, and may repre sent a novel mode of exon regulation.