Myogenic factors that regulate expression of muscle-specific, microRNAs
Myogenic factors that regulate expression of muscle-specific, microRNAs
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DOI：
10.1073/pnas.0602831103
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发表时间：
2006-06-06
影响因子：
11.1
通讯作者：
Lodish, Harvey F.
中科院分区：
文献类型：
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作者：
Rao, Prakash K.;Kumar, Roshan M.;Lodish, Harvey F.
自从微小RNA（microRNAs）被发现是动物早期发育的关键调节因子以来，它们现在被公认为是基因表达的广泛调节因子。尽管它们数量丰富，但对于微小RNA生物发生的调控却知之甚少。我们发现，在原代人类成肌细胞以及小鼠间充质C2C12干细胞系中，三种高度保守的肌肉特异性微小RNA，即miR - 1、miR - 133和miR - 206，在成肌细胞 - 肌管转化过程中被强烈诱导。在C2C12细胞的成骨转化过程中，这些微小RNA未被诱导。此外，编码miR - 1的两个基因座（miR - 1 - 1和miR - 1 - 2）以及编码miR - 133的三个基因座中的两个（miR - 133a - 1和miR - 133a - 2）在肌生成过程中被强烈诱导。一些被诱导的微小RNA位于基因间区域，而有两个则是从与其所嵌入的非肌肉特异性基因相反的方向转录。通过染色质免疫沉淀（CHIP）分析，我们证明了生肌因子肌细胞生成素（Myogenin）和肌分化因子（MyoD）与这些微小RNA上游区域结合，因此很可能调节它们的表达。由于miR - 1和miR - 206被预测会抑制相似的信使RNA（mRNA）靶点，我们的工作表明这些微小RNA的诱导对于调节肌肉特异性蛋白质的表达非常重要。
Since their discovery as key regulators of early animal development, microRNAs now are recognized as widespread regulators of gene expression. Despite their abundance, little is known regarding the regulation of microRNA biogenesis. We show that three highly conserved muscle-specific microRNAs, miR-1, miR-133 and miR-206, are robustly induced during the myoblast-myotube transition, both in primary human myoblasts and in the mouse mesenchymal C2C12 stem cell line. These microRNAs were not induced during osteogenic conversion of C2C12 cells. Moreover, both loci encoding miR-1, miR-1-1, and miR-1-2, and two of the three encoding miR-133, miR-133a-1 and miR-133a-2, are strongly induced during myogenesis. Some of the induced microRNAs are in intergenic regions, whereas two are transcribed in the opposite direction to the nonmuscle-specific gene in which they are embedded. By using CHIP analysis, we demonstrate that the myogenic factors Myogenin and MyoD bind to regions upstream of these microRNAs and, therefore, are likely to regulate their expression. Because miR-1 and miR-206 are predicted to repress similar mRNA targets, our work suggests that induction of these microRNAs is important in regulating the expression of muscle-specific proteins.