Coordinate Regulation of Transcription and Splicing by Steroid Receptor Coregulators

• Published in: Science (American Association for the Advancement of Science) Vol. 298; no. 5592; pp. 416 - 419
• Main Authors: Auboeuf, Didier, Hönig, Arnd, Berget, Susan M., O'Malley, Bert W.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 11.10.2002; The American Association for the Advancement of Science
• Subjects: Alternative Splicing; Animals; Biological and medical sciences; Calcitonin - genetics; Calcitonin Gene-Related Peptide - genetics; Carrier Proteins - metabolism; COS Cells; Dexamethasone - metabolism; Dexamethasone - pharmacology; Estradiol - metabolism; Estradiol - pharmacology; Estrogen Receptor alpha; Estrogen Receptor beta; Exons; Fundamental and applied biological sciences. Psychology; Genes; Genes, Reporter; HeLa Cells; Hormones; Human genetics; Humans; Hyaluronan Receptors - genetics; Intracellular Signaling Peptides and Proteins; Messenger RNA; Molecular and cellular biology; Molecular genetics; Mutation; Progesterone - metabolism; Progesterone - pharmacology; Promoter Regions, Genetic; Protein Structure, Tertiary; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Receptors, Glucocorticoid - metabolism; Receptors, Progesterone - metabolism; Response Elements; Ribonucleic acid; RNA; RNA Helicases - metabolism; RNA-Binding Protein FUS - metabolism; Site Selection; Splicing; Steroid hormones; Steroid receptors; Steroids; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional regulatory elements; Transfection; Tumor Cells, Cultured; Steroid; Regulation(control); Receptor protein; Regulator; Splicing; Transcription; Non-programmatic
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1073734

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.