Coordinate regulation of transcription and splicing by steroid receptor coregulators.
Recent observations indicating that promoter identity influences alternative RNA-processing decisions have created interest in the regulatory interactions between RNA polymerase II transcription and precursor messenger RNA (pre-mRNA) processing. We examined the impact of steroid receptor-mediated transcription on RNA processing with reporter genes subject to alternative splicing driven by steroid-sensitive promoters. Steroid hormones affected the processing of pre-mRNA synthesized from steroid-sensitive promoters, but not from steroid-unresponsive promoters, in a steroid receptor-dependent and receptor-selective manner. Several nuclear receptor coregulators showed differential splicing effects, suggesting that steroid hormone receptors may simultaneously control gene transcription activity and exon content of the product mRNA by recruiting coregulators involved in both processes.
Auboeuf
Didier
D
Department of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hönig
Arnd
A
Berget
Susan M
SM
O'Malley
Bert W
BW
D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002116:Calcitonin / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005091:Exons; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020218:Response Elements; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; C436317:RBM14 protein, human; D034702:RNA-Binding Protein FUS; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D002116:Calcitonin; D020365:RNA Helicases; D015740:Calcitonin Gene-Related Peptide