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Abstract
Changes in promoter structure and occupation have been shown to modify the splicing
pattern of several genes, evidencing a coupling between transcription and alternative
splicing. It has been proposed that the promoter effect involves modulation of RNA
pol II elongation rates. The C4 point mutation of the Drosophila pol II largest subunit
confers on the enzyme a lower elongation rate. Here we show that expression of a human
equivalent to Drosophila's C4 pol II in human cultured cells affects alternative splicing
of the fibronectin EDI exon and adenovirus E1a pre-mRNA. Most importantly, resplicing
of the Hox gene Ultrabithorax is stimulated in Drosophila embryos mutant for C4, which
demonstrates the transcriptional control of alternative splicing on an endogenous
gene. These results provide a direct proof for the elongation control of alternative
splicing in vivo.