Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD
Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD
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长非编码 RNA Linc-RAM 通过与 MyoD 相互作用增强肌原分化
DOI：
10.1038/ncomms14016
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发表时间：
2017-01-16
影响因子：
16.6
通讯作者：
Zhu, Dahai
中科院分区：
文献类型：
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作者：
Yu, Xiaohua;Zhang, Yong;Zhu, Dahai
长链非编码RNA（lncRNA）是多种生物过程的重要调节因子。本文报道了一种新的长基因间非编码RNA的功能鉴定和表征，该RNA具有MyoD调节和骨骼肌限制性表达，可促进成肌程序的激活，因此被称为Linc-RAM（Linc-RNA Activator of Myogenesis）。Linc-RAM是从成肌细胞的基因间区域转录的，其表达在成肌过程中上调。值得注意的是，在体内功能研究表明，Linc-RAM基因敲除小鼠显示受损的肌肉再生由于卫星细胞的分化缺陷。从机制上讲，Linc-RAM通过直接结合MyoD来调节生肌基因的表达，MyoD反过来又促进MyoD-Baf 60 c-Brg 1复合物在靶基因的调控元件上的组装。总的来说，我们的研究结果揭示了谱系特异性Linc-RAM作为组织特异性染色质重塑和基因表达所需的调控lncRNA的功能作用和分子机制。
Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis).Linc-RAMis transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably,in vivofunctional studies show thatLinc-RAMknockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells. Mechanistically, Linc-RAM regulates expression of myogenic genes by directly binding MyoD, which in turn promotes the assembly of the MyoD–Baf60c–Brg1 complex on the regulatory elements of target genes. Collectively, our findings reveal the functional role and molecular mechanism of a lineage-specific Linc-RAM as a regulatory lncRNA required for tissues-specific chromatin remodelling and gene expression.