ALTERNATIVE SPLICING OF THE FIBRONECTIN EIIIB EXON DEPENDS ON SPECIFIC TGCATG REPEATS

The fibronectin EIIIB exon is alternatively spliced in a cell-type-spe cific manner, and TGCATG repeats in the intron downstream of EIIIB hav e been implicated in this regulation, Analysis of the intron sequence from several vertebrates shows that the pattern of repeats in the 3' h alf of the intron is evolutionarily conserved. Point mutations in cert ain highly conserved repeats greatly reduce EIIIB inclusion, suggestin g that a multicomponent complex may recognize the repeats. Expression of the SR protein SRp40, SRp20, or ASF/SF2 stimulates EIIIB inclusion. Studies of the interplay between mutations in the repeats and SRp40-s timulated inclusion suggest that the repeats are recognized in many, i f not all, cell types, and that EIIIB inclusion may be regulated by qu antitative changes in multiple factors.