CONSERVED INTRON ELEMENTS REPRESS SPLICING OF A NEURON-SPECIFIC C-SRCEXON IN-VITRO

The neuron-specific N1 exon of the mouse c-src transcript is normally skipped in nonneuronal cells. In this study, we examined the sequence requirements for the exclusion of this exon in nonneuronal HeLa cell n uclear extracts. We found that the repression of the N1 exon is mediat ed by specific intron sequences that flank the N1 exon. Mutagenesis ex periments identified conserved CUCUCU elements within these intron reg ions that are required for the repression of N1 splicing. The addition of an RNA competitor containing the upstream regulatory sequence to t he HeLa extract induced splicing of the intron downstream of N1, indic ating that the competitor sequence binds to splicing repressor protein s. The similarities between this mechanism for are splicing repression and the repression of other regulated exons point to a common role of exon-spanning interactions in splicing repression.