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Distal regulation of alternative splicing by splicing enhancer in equine ß-casein intron 1
Lenasi, Tina ; Peterlin, Matija Boris ; Dovč, Peter, 1958-
The complexity of cotranscriptional splicing is reflected in the coordinated interplay between various cis-elements and transacting factors. In this report, we demonstrated that a cis-element in ...intron 1 of the equine ß-casein gene (intronic splicing enhancer 1, ISE1) increases the inclusion of all weak exon in uts pre-mRNA. The ISE1 also functioned on a hybrid tranbscript, which was transcribed from the [alfa]-globin promoter, where it increased the inclusion of the human fibronectin EDA exon and the ß-casein exon 5. The region of ISE1 necessary for its function included the same sequence as is found in some exonic splicing enhancers. Since tha ISE1 influenced the splicing of the entire transcript from intron 1, we propose a model for the cotranscriptional splicing, of ß-casein mRNA, where the 5' end of the growing transcript remains associated with the C-terminal domain of RNA polymerase II.Thus, the ISE1 remains in close proximity to the mRNA exit groove throughout transcription and influences all weak exons as soon as they are copied.
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