Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Genes Dev. 2010 Apr 1;24(7):653-8. doi: 10.1101/gad.1894310. Epub 2010 Mar 18.
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.
最近的研究发现，可变剪接事件是脊椎动物心脏在出生后发育过程中重塑的一个保守组成部分。在这里，我们报告说，Dicer 的靶向缺失，特别是在成年小鼠心肌中，揭示了 microRNAs（miRNAs）在调节出生后剪接事件的网络以及维持成年剪接程序中的作用。我们证明了 miR-23a/b 在 CUGBP 和 ETR-3 样因子（CELF）蛋白的急剧出生后下调中的直接作用，这些蛋白调节心脏中近一半的发育调控剪接事件。这些发现定义了一个层次结构，其中特定 miRNAs 的快速出生后上调控制着替代剪接调节剂的表达，以及随后其下游靶标的剪接事件。
