title: Transcriptional activators control splicing and 3'-end cleavage levels.
abstract: 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.
authors.affiliation: Banting and Best Department of Medical Research and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Rosonina
authors.forename: Malina A
authors.initials: MA
authors.lastname: Bakowski
authors.forename: Susan
authors.initials: S
authors.lastname: McCracken
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000378:metabolism; D006801:Humans; D007438:Introns; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D005047:Etoposide; D012319:RNA Polymerase II; D012260:Ribonucleases