Generation of alternative Ultrabithorax isoforms and stepwise removal of a large intron by resplicing at exon-exon junctions.

Little is known about mechanisms that regulate and ensure accurate processing of complex transcription units with long introns. We investigate this in the Ultrabithorax gene of Drosophila. A consensus 5' splice site is regenerated at the junction between the first exon and a small internal exon (mI); this splice site is used in a developmentally regulated manner to remove mI during subsequent processing of the downstream intron. Conserved elements within mI and an interaction with exon mII modulate use of the regenerated splice site. Structural similarities predict the same process for mII. This resplicing mechanism avoids competition between distant splice sites for control of exon inclusion and allows removal of a 74 kb intron as a series of smaller fragments.