MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development
Auinash Kalsotra , Kun Wang , Pei-Feng Li , and Thomas A. Cooper
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.