A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart
- Douglas M. Anderson1,2,5,
- Kelly M. Anderson1,2,5,
- Benjamin R. Nelson2,3,
- John R. McAnally2,3,
- Svetlana Bezprozvannaya2,3,
- John M. Shelton4,
- Rhonda Bassel-Duby2,3 and
- Eric N. Olson2,3
- 1Department of Medicine, Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, New York 14642, USA;
- 2Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 3Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 4Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
- Corresponding authors: doug_anderson{at}urmc.rochester.edu, eric.olson{at}utsouthwestern.edu
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↵5 These authors contributed equally to this work.
Abstract
Myocardin, a potent coactivator of serum response factor (SRF), competes with ternary complex factor (TCF) proteins for SRF binding to balance opposing mitogenic and myogenic gene programs in cardiac and smooth muscle. Here we identify a cardiac lncRNA transcribed adjacent to myocardin, named CARDINAL, which antagonizes SRF-dependent mitogenic gene transcription in the heart. CARDINAL-deficient mice show ectopic TCF/SRF-dependent mitogenic gene expression and decreased cardiac contractility in response to age and ischemic stress. CARDINAL forms a nuclear complex with SRF and inhibits TCF-mediated transactivation of the promitogenic gene c-fos, suggesting CARDINAL functions as an RNA cofactor for SRF in the heart.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.348304.121.
- Received January 20, 2021.
- Accepted April 9, 2021.
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