Journal
GENES & DEVELOPMENT
Volume 24, Issue 7, Pages 653-658Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1894310
Keywords
Alternative splicing networks; CELFproteins; heart development; microRNA
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Funding
- NIH [R01GM076493]
- Myotonic Dystrophy Foundation
- NNSFC [G30730045]
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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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