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Science 298 (5592): 416-419

Copyright © 2002 by the American Association for the Advancement of Science

Coordinate Regulation of Transcription and Splicing by Steroid Receptor Coregulators

Didier Auboeuf,1 Arnd Hönig,2* Susan M. Berget,2 Bert W. O'Malley1dagger

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.

1 Department of Molecular and Cellular Biology,
2 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
*   Present address: Department of Obstetrics and Gynecology, University of Tubingen, 72076 Tubingen, Germany.

dagger    To whom correspondence should be addressed. E-mail: berto{at}

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 285, 15220-15233
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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A. L. Amelio, M. Caputi, and M. D. Conkright (2009)
EMBO J. 28, 2733-2747
   Abstract »    Full Text »    PDF »
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Dis. Model. Mech. 2, 500-507
   Abstract »    Full Text »    PDF »
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J. Yang and M. J Young (2009)
J. Mol. Endocrinol. 43, 53-64
   Abstract »    Full Text »    PDF »
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A J Tyson-Capper, E A Shiells, and S C Robson (2009)
J. Mol. Endocrinol. 43, 29-41
   Abstract »    Full Text »    PDF »
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S. Pauklin, I. V. Sernandez, G. Bachmann, A. R. Ramiro, and S. K. Petersen-Mahrt (2009)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. I. Young, E. P. Hong, J. C. Castle, J. Crespo-Barreto, A. B. Bowman, M. F. Rose, D. Kang, R. Richman, J. M. Johnson, S. Berget, et al. (2005)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Role for PSF in Mediating Transcriptional Activator-Dependent Stimulation of Pre-mRNA Processing In Vivo.
E. Rosonina, J. Y. Y. Ip, J. A. Calarco, M. A. Bakowski, A. Emili, S. McCracken, P. Tucker, C. J. Ingles, and B. J. Blencowe (2005)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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D. Auboeuf, D. H. Dowhan, M. Dutertre, N. Martin, S. M. Berget, and B. W. O'Malley (2005)
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   Full Text »    PDF »
Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.
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   Abstract »    Full Text »    PDF »
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M. Esslimani-Sahla, A. Kramar, J. Simony-Lafontaine, M. Warner, J.-A. Gustafsson, and H. Rochefort (2005)
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   Abstract »    Full Text »    PDF »
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J. K. Lamba, V. Lamba, K. Yasuda, Y. S. Lin, M. Assem, E. Thompson, S. Strom, and E. Schuetz (2004)
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   Abstract »    Full Text »    PDF »
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RNA 10, 1489-1498
   Abstract »    Full Text »    PDF »
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H. Zhang, S.-Q. Kuang, L. Liao, S. Zhou, and J. Xu (2004)
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   Abstract »    Full Text »    PDF »
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I. Pfeifer, C. Anderson, R. Werner, and E. Oltra (2004)
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   Abstract »    Full Text »    PDF »
U2AF homology motifs: protein recognition in the RRM world.
C. L. Kielkopf, S. Lucke, and M. R. Green (2004)
Genes & Dev. 18, 1513-1526
   Abstract »    Full Text »    PDF »
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M. Elkin, A. Orgel, and H. K. Kleinman (2004)
J Natl Cancer Inst 96, 875-878
   Abstract »    Full Text »    PDF »
High-throughput polyribosome fractionation.
Y. Wang, S. Ringquist, A. H. Cho, G. Rondeau, and J. Welsh (2004)
Nucleic Acids Res. 32, e79
   Abstract »    Full Text »    PDF »
Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element.
G.-P. Zhou, C. Wong, R. Su, S. C. Crable, K. P. Anderson, and P. G. Gallagher (2004)
Blood 103, 4302-4309
   Abstract »    Full Text »    PDF »
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D. Auboeuf, D. H. Dowhan, Y. K. Kang, K. Larkin, J. W. Lee, S. M. Berget, and B. W. O'Malley (2004)
PNAS 101, 2270-2274
   Abstract »    Full Text »    PDF »
A novel RING-finger-like protein Ini1 is essential for cell cycle progression in fission yeast.
E. Oltra, F. Verde, R. Werner, and G. D'Urso (2004)
J. Cell Sci. 117, 967-974
   Abstract »    Full Text »    PDF »
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D. Auboeuf, D. H. Dowhan, X. Li, K. Larkin, L. Ko, S. M. Berget, and B. W. O'Malley (2004)
Mol. Cell. Biol. 24, 442-453
   Abstract »    Full Text »    PDF »
Influence of Polymerase II Processivity on Alternative Splicing Depends on Splice Site Strength.
G. Nogues, M. J. Munoz, and A. R. Kornblihtt (2003)
J. Biol. Chem. 278, 52166-52171
   Abstract »    Full Text »    PDF »
Hepatic CYP2B6 Expression: Gender and Ethnic Differences and Relationship to CYP2B6 Genotype and CAR (Constitutive Androstane Receptor) Expression.
V. Lamba, J. Lamba, K. Yasuda, S. Strom, J. Davila, M. L. Hancock, J. D. Fackenthal, P. K. Rogan, B. Ring, S. A. Wrighton, et al. (2003)
J. Pharmacol. Exp. Ther. 307, 906-922
   Abstract »    Full Text »    PDF »
Transcriptional Activators Control Splicing and 3'-End Cleavage Levels.
E. Rosonina, M. A. Bakowski, S. McCracken, and B. J. Blencowe (2003)
J. Biol. Chem. 278, 43034-43040
   Abstract »    Full Text »    PDF »
Unfolding the Action of Progesterone Receptors.
X. Li and B. W. O'Malley (2003)
J. Biol. Chem. 278, 39261-39264
   Full Text »    PDF »
An Sp1-NF-Y/Progesterone Receptor DNA Binding-dependent Mechanism Regulates Progesterone-induced Transcriptional Activation of the Rabbit RUSH/SMARCA3 Gene.
A. Hewetson and B. S. Chilton (2003)
J. Biol. Chem. 278, 40177-40185
   Abstract »    Full Text »    PDF »
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C. Zhang, D. R. Dowd, A. Staal, C. Gu, J. B. Lian, A. J. van Wijnen, G. S. Stein, and P. N. MacDonald (2003)
J. Biol. Chem. 278, 35325-35336
   Abstract »    Full Text »    PDF »
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S. Savaldi-Goldstein, D. Aviv, O. Davydov, and R. Fluhr (2003)
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   Abstract »    Full Text »    PDF »
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F. Pagani, C. Stuani, E. Zuccato, A. R. Kornblihtt, and F. E. Baralle (2003)
J. Biol. Chem. 278, 1511-1517
   Abstract »    Full Text »    PDF »
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E. M. Adler, N. R. Gough, and L. B. Ray (2003)
Sci. STKE 2003, eg1
   Full Text »    PDF »

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