RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20.
Previous studies have linked the C-terminal domain (CTD) of RNA polymerase II (pol II) with cotranscriptional precursor messenger RNA processing, but little is known about the CTD's function in regulating alternative splicing. We have examined this function using alpha-amanitin-resistant pol II CTD mutants and fibronectin reporter minigenes. We found that the CTD is required for the inhibitory action of the serine/arginine-rich (SR) protein SRp20 on the inclusion of a fibronectin cassette exon in the mature mRNA. CTD phosphorylation controls transcription elongation, which is a major contributor to alternative splicing regulation. However, the effect of SRp20 is still observed when transcription elongation is reduced. These results suggest that the CTD promotes exon skipping by recruiting SRp20 and that this contributes independently of elongation to the transcriptional control of alternative splicing.
de la Mata
Manuel
M
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.
Kornblihtt
Alberto R
AR
D017398:Alternative Splicing; D000546:Amanitins / Q000494:pharmacology; D045744:Cell Line, Tumor; D005091:Exons; D005353:Fibronectins / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D000068103:Serine-Arginine Splicing Factors; D014158:Transcription, Genetic; D014162:Transfection
D000546:Amanitins; D005353:Fibronectins; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors; D012319:RNA Polymerase II