MyoD-induced circular RNA CDR1as promotes myogenic differentiation of skeletal muscle satellite cells
MyoD-induced circular RNA CDR1as promotes myogenic differentiation of skeletal muscle satellite cells
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MyoD诱导的环状RNA CDR1as促进骨骼肌卫星细胞的生肌分化
DOI：
10.1016/j.bbagrm.2019.07.001
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发表时间：
2019-08-01
影响因子：
4.7
通讯作者：
Zhang, Hongping
中科院分区：
文献类型：
--
作者：
Li, Li;Chen, Yuan;Zhang, Hongping
许多蛋白质编码基因和非编码基因在控制骨骼肌形成中相互作用。然而，与线性转录物相比，共价闭合环状RNA（circRNA）作为调控非编码RNA（ncRNA）分子的新前沿，其功能仍不清楚。在这里，我们确定了CDR 1as（小脑变性相关蛋白1转录物的反义，也称为ciRS-7），一种众所周知的癌症和神经元circRNA，在实际控制肌肉分化中起着重要作用。CDR 1as在胚胎中期的山羊胎儿的肌肉中高度表达，并且在体外成肌分化的起始时被激活。MyoD（myogenic differentiation protein 1）是一种肌细胞生成的转录驱动因子，通过结合在其5'侧翼区（-646至-634 bp，邻近预测的转录起始位点-580 bp）来促进CDR 1as。CDR 1as的过表达或敲低分别显著诱导或阻碍肌肉分化程序。通过与miR-7（microRNA 7）竞争性结合，CDR 1as缓解由miR-7引起的IGF 1 R（胰岛素样生长因子1受体）的下调，从而激活肌肉分化。这些结果揭示了CDR 1as在肌源性分化中起关键作用，这扩展了CDR 1as在哺乳动物发育和疾病中的多功能。
Many protein coding and non-coding genes interplay in governing skeletal muscle formation. Nevertheless, comparing with the linear transcripts, functions of covalently closed circular RNAs (circRNAs), the new frontier of regulatory non-coding RNA (ncRNAs) molecules, remain largely unknown. Here, we identify CDR1as (antisense to the cerebellar degeneration-related protein 1 transcript, also termed as ciRS-7), a well-known cancer and neuron circRNA, plays a significant role in virtually controlling muscle differentiation. CDR1as is highly expressed in muscles of the mid-embryonic goat foetus, and activated at the initiation of myogenic differentiation in vitro. MyoD (myogenic differentiation protein 1), a driven transcription factor for myogenesis, promotes CDR1as by binding on its 5' flank region (- 646 to -634 bp, neighbouring the predicted transcription start site at - 580 bp). Overexpression or knockdown of CDR1as dramatically induces or impedes muscle differentiation program, respectively. By competitively binding to miR-7 (microRNA 7), CDR1as relieves the downregulation of IGF1R (insulin like growth factor 1 receptor) caused by miR-7 and consequently activates muscle differentiation. These results unveil that CDR1as plays critical roles in myogenic differentiation, which extends the versatile functions of CDR1as in mammal development and disease.