由肌球蛋白基因编码的一族微小RNA调控着肌球蛋白的表达及肌肉性能。
A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance.
作者信息
van Rooij Eva, Quiat Daniel, Johnson Brett A, Sutherland Lillian B, Qi Xiaoxia, Richardson James A, Kelm Robert J, Olson Eric N
机构信息
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
出版信息
Dev Cell. 2009 Nov;17(5):662-73. doi: 10.1016/j.devcel.2009.10.013.
Myosin is the primary regulator of muscle strength and contractility. Here we show that three myosin genes, Myh6, Myh7, and Myh7b, encode related intronic microRNAs (miRNAs), which, in turn, control muscle myosin content, myofiber identity, and muscle performance. Within the adult heart, the Myh6 gene, encoding a fast myosin, coexpresses miR-208a, which regulates the expression of two slow myosins and their intronic miRNAs, Myh7/miR-208b and Myh7b/miR-499, respectively. miR-208b and miR-499 play redundant roles in the specification of muscle fiber identity by activating slow and repressing fast myofiber gene programs. The actions of these miRNAs are mediated in part by a collection of transcriptional repressors of slow myofiber genes. These findings reveal that myosin genes not only encode the major contractile proteins of muscle, but act more broadly to influence muscle function by encoding a network of intronic miRNAs that control muscle gene expression and performance.
肌球蛋白是肌肉力量和收缩性的主要调节因子。我们在此表明，三个肌球蛋白基因Myh6、Myh7和Myh7b编码相关的内含子微小RNA（miRNA），这些miRNA反过来控制肌肉肌球蛋白含量、肌纤维类型以及肌肉性能。在成年心脏中，编码快速肌球蛋白的Myh6基因共表达miR-208a，miR-208a分别调节两种慢速肌球蛋白及其内含子miRNA（Myh7/miR-208b和Myh7b/miR-499）的表达。miR-208b和miR-499通过激活慢速肌纤维基因程序并抑制快速肌纤维基因程序，在肌纤维类型的决定中发挥冗余作用。这些miRNA的作用部分由一组慢速肌纤维基因的转录抑制因子介导。这些发现表明，肌球蛋白基因不仅编码肌肉的主要收缩蛋白，还通过编码一个控制肌肉基因表达和性能的内含子miRNA网络，更广泛地影响肌肉功能。
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