PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element
- Alexander K. Ebralidze1,
- Florence C. Guibal1,
- Ulrich Steidl2,
- Pu Zhang1,
- Sanghoon Lee1,
- Boris Bartholdy1,
- Meritxell Alberich Jorda1,
- Victoria Petkova1,
- Frank Rosenbauer3,
- Gang Huang1,
- Tajhal Dayaram1,
- Johanna Klupp1,
- Karen B. O’Brien1,
- Britta Will1,
- Maarten Hoogenkamp4,
- Katherine L.B. Borden5,
- Constanze Bonifer4,6, and
- Daniel G. Tenen1,6,7
- 1 Harvard Institutes of Medicine, Harvard Stem Cell Institute, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA;
- 2 Department of Cell Biology and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA;
- 3 Max-Delbruck-Center for Molecular Medicine, Berlin 13092, Germany;
- 4 Leeds Institute for Molecular Medicine, St James’s University Hospital, University of Leeds, Leeds LS7 4JS, United Kingdom;
- 5 Department of Pathology and Cell Biology and Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3T 1J4, Canada
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↵6 These authors contributed equally to this work.
Abstract
The transcription factor PU.1 is an important regulator of hematopoiesis; precise expression levels are critical for normal hematopoietic development and suppression of leukemia. We show here that noncoding antisense RNAs are important modulators of proper dosages of PU.1. Antisense and sense RNAs are regulated by shared evolutionarily conserved cis-regulatory elements, and we can show that antisense RNAs inhibit PU.1 expression by modulating mRNA translation. We propose that such antisense RNAs will likely be important in the regulation of many genes and may be the reason for the large number of overlapping complementary transcripts with so far unknown function.
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Footnotes
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↵7 Corresponding author.
↵7 E-MAIL dtenen{at}bidmc.harvard.edu; FAX (617) 667-3299.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1654808.
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- Received January 23, 2008.
- Accepted June 16, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
