The steroid receptor RNA activator protein is recruited to promoter regions and acts as a transcriptional repressor

Chooniedass-Kothari, Shilpa; Hamedani, Mohammad K.; Auge, Carole; Wang, Xuemei; Carascossa, Sophie; Yan, Yi; Cooper, Charlton; Vincett, Daniel; Myal, Yvonne; Jalaguier, Stephan; Cavailles, Vincent; Leygue, Etienne

doi:10.1016/j.febslet.2010.04.022

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Volume 584, Issue 11 , Pages 2218-2224, 3 June 2010

The steroid receptor RNA activator protein is recruited to promoter regions and acts as a transcriptional repressor

Edited by Ivan Sadowski

Shilpa Chooniedass-Kothari
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Mohammad K. Hamedani
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Carole Auge
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Xuemei Wang
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Sophie Carascossa
- University of Montpellier, INSERM U148 Hormones and Cancer, Montpellier, France
Yi Yan
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Charlton Cooper
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Daniel Vincett
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Yvonne Myal
- University of Manitoba, Department of Physiology, Winnipeg, Manitoba, Canada
Stephan Jalaguier
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Vincent Cavailles
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
Etienne Leygue
- University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Manitoba, Canada
- Manitoba Institute of Cell Biology (MICB), Winnipeg, Manitoba, Canada
- Corresponding author. Address: Department of Biochemistry and Medical Genetics, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E0W3. Fax: +1 204 789 3900.

Received 3 March 2010; received in revised form 31 March 2010; accepted 8 April 2010. published online 14 April 2010.

Abstract

Products of the steroid receptor RNA activator (SRA1) gene have the unusual property to function both at the RNA and the protein levels. SRA-RNA has long been known to increase the activity of multiple nuclear receptors. It has more recently been proposed than steroid receptor RNA activator protein (SRAP) also modulates steroid receptors activity. Herein, we show for the first time that SRAP physically interacts with multiple transcription factors and is recruited to specific promoter regions. Artificially recruiting SRAP to the promoter of a luciferase reporter gene under the control of the strong transcriptional activator VP16 leads to a decrease in transcription. Altogether we propose that SRAP could be a new transcriptional regulator, able to function as a repressor through direct association with promoters.

Structured summary

MINT-7761068: SRAP (uniprotkb:Q9HD15) physically interacts (MI:0915) with HDAC2 (uniprotkb:Q92769) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: SRA, steroid receptor RNA activator, SRAP, steroid receptor RNA activator protein, HDAC, histone de-acetylase, TSA, trichostatin A

Keywords: Steroid receptor RNA activator, Steroid receptor RNA activator protein, Transcriptional repressor