The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation
The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation
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DOI：
10.1038/ng1725
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发表时间：
2006-02-01
期刊：
影响因子：
30.8
通讯作者：
Wang, DZ
中科院分区：
文献类型：
--
作者：
Chen, JF;Mandel, EM;Wang, DZ
了解调节细胞增殖和分化的分子机制是发育生物学的核心主题。 microRNA（miRNA）是一类与22种核苷酸相似的调节性RNA，这些核苷酸在转录后调节基因表达（1,2）。增加证据表明miRNA在各种生物过程中的潜在作用（3-8）。在这里，我们表明miRNA-1（miR-1）和miRNA-133（miR-133）聚集在同一染色体基因座上，在发育过程中以组织特异性方式转录在一起。 miR-1和miR-133在体外和Xenopus laevis胚胎体内调节骨骼肌肉增殖和分化中具有不同的作用。 miR-1通过靶向组蛋白脱乙酰基酶4（HDAC4）（肌肉基因表达的转录阻遏物）来促进肌发生。相比之下，miR-133通过抑制血清反应因子（SRF）增强了肌细胞增殖。我们的结果表明，两个成熟的miRNA来自相同的miRNA多生殖器并共同转录，可以执行不同的生物学功能。我们的研究一起提出了一种分子机制，其中miRNA参与控制骨骼肌基因表达和胚胎发育的转录回路。
Understanding the molecular mechanisms that regulate cellular proliferation and differentiation is a central theme of developmental biology. MicroRNAs ( miRNAs) are a class of regulatory RNAs of similar to 22 nucleotides that post-transcriptionally regulate gene expression(1,2). Increasing evidence points to the potential role of miRNAs in various biological processes(3-8). Here we show that miRNA-1 (miR-1) and miRNA- 133 (miR-133), which are clustered on the same chromosomal loci, are transcribed together in a tissue-specific manner during development. miR-1 and miR-133 have distinct roles in modulating skeletal muscle proliferation and differentiation in cultured myoblasts in vitro and in Xenopus laevis embryos in vivo. miR-1 promotes myogenesis by targeting histone deacetylase 4 (HDAC4), a transcriptional repressor of muscle gene expression. By contrast, miR-133 enhances myoblast proliferation by repressing serum response factor (SRF). Our results show that two mature miRNAs, derived from the same miRNA polycistron and transcribed together, can carry out distinct biological functions. Together, our studies suggest a molecular mechanism in which miRNAs participate in transcriptional circuits that control skeletal muscle gene expression and embryonic development.