Transcriptional activators control splicing and 3′-end cleavage levels

We have investigated whether transcriptional activators influence the efficiency of constitutive splicing and 3'-end formation, in addition to transcription levels. Remarkably, strong activators result in higher levels of splicing and 3'-cleavage than weak activators and can control the efficiency of these steps in pre-mRNA processing separately. The pre-mRNA processing stimulatory property of activators is dependent on their binding to promoters, but is not an indirect consequence of the levels of transcripts produced. Moreover, stimulation of splicing and cleavage by a strong activator operates by a mechanism that requires the carboxyl-terminal domain of RNA polymerase II. The splicing stimulatory property of activators was observed for unrelated transcripts and for separate introns within a transcript, indicating a possible general role for strong activators in facilitating pre-mRNA processing levels. The results suggest that the efficiency of constitutive splicing and 3'-end cleavage is closely coordinated with transcription levels by promoter-bound activators.