Nascent transcripts are the true substrates for many splicing events in 
mammalian cells. In this review we discuss transcription, splicing, and 
alternative splicing in the context of co-transcriptional processing of 
pre-mRNA. The realization that splicing occurs co-transcriptionally requires two 
important considerations: First, the cis-acting elements in the splicing 
substrate are synthesized at different times in a 5' to 3' direction. This 
dynamic view of the substrate implies that in a 100 kb intron the 5' splice site 
will be synthesized as much as an hour before the 3' splice site. Second, the 
transcription machinery and the splicing machinery, which are both complex and 
very large, are working in close proximity to each other. It is therefore likely 
that these two macromolecular machines interact, and recent data supporting this 
notion is discussed. We propose a model for co-transcriptional pre-mRNA 
processing that incorporates the concepts of splice site-tethering and dynamic 
exon definition. Also, we present a dynamic view of the alternative splicing of 
FGF-R2 and suggest that this view could be generally applicable to many 
regulated splicing events.