REGULATION OF ALTERNATIVE PRE-MESSENGER-RNA SPLICING BY A NOVEL REPEATED HEXANUCLEOTIDE ELEMENT

The alternatively spliced exon EIIIB is regulated in a cell type-speci fic manner in the rat fibronectin gene. Splicing of EIIIB into fibrone ctin mRNA is dependent on sequences in the intron immediately downstre am of EIIIB. We show that a short, highly repeated TGCATG motif in thi s intron is important for cell type-specific recognition of EIIIB as a n exon. This motif enhances usage of the EIIIB 5' splice site; further more, this repeated TGCATG sequence can activate an alternatively spli ced exon in the unrelated rat preprotachykinin pre-mRNA. Interestingly , this sequence can also be found within cis-acting elements identifie d previously in other alternatively spliced genes. This short repeated TGCATG motif is therefore a cell type-specific element that, in addit ion to controlling fibronectin alternative splicing, may participate i n the regulation of other alternative RNA processing events.