Intronic UGG repeats coordinate splicing of CD44 alternative exons v8 and v9.

Alternative CD44 exons v8, v9, and v10 are spliced as a block in epithelial cells (for example SVK14 cells), but can be skipped as a block by other cells. Using a minigene approach, we show that downstream intronic UGG repeats participate in activation of v8 exon splicing in SVK14 cells. The repeats can activate splicing of a heterologous exon in SVK14 cells and act additively with a previously described v8 exon splicing enhancer in this context. An alternative v9 exon 5' splice site used by some cells to make an aberrant transcript is repressed by an immediately downstream (UGG)3 sequence in SVK14 cells. We conclude that UGG repeats both activate v8 exon splicing and repress use of the alternative v9 exon 5' splice site in SVK14 cells, thus participating in the coordination of correct epithelial cell splicing of the v8-10 block.