MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development
- 1Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA;
- 2Division of Cardiovascular Research, National Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
- 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
Abstract
Alternative splicing transitions have been identified recently as a conserved component of vertebrate heart remodeling during postnatal development. Here we report that the targeted deletion of Dicer, specifically in adult mouse myocardium, reveals the role of microRNAs (miRNAs) in regulating networks of postnatal splicing transitions and in maintaining adult splicing programs. We demonstrate a direct role for miR-23a/b in the dramatic postnatal down-regulation of CUGBP and ETR-3-like factor (CELF) proteins that regulate nearly half of developmentally regulated splicing transitions in the heart. These findings define a hierarchy in which rapid postnatal up-regulation of specific miRNAs controls expression of alternative splicing regulators and the subsequent splicing transitions of their downstream targets.
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Footnotes
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↵4 Corresponding author.
E-MAIL tcooper{at}bcm.edu; FAX (713) 798-5838.
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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.1894310.
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Supplemental material is available at http://www.genesdev.org.
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- Received December 7, 2009.
- Accepted February 17, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
