MIR-206 regulates connexin43 expression during skeletal muscle development.
MIR-206 regulates connexin43 expression during skeletal muscle development.
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DOI：
10.1093/nar/gkl743
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发表时间：
2006
影响因子：
14.9
通讯作者：
Werner R
中科院分区：
文献类型：
--
作者：
Anderson C;Catoe H;Werner R
成肌细胞体外融合需要连接蛋白43（Cx43）间隙连接通道的表达。然而，在体外和体内成肌细胞融合开始后，缝隙连接迅速下调。在这项研究中，我们表明，这种下调是由两个相关的microRNA，miR-206和miR-1，抑制在成肌细胞分化过程中的Cx43蛋白的表达，而不改变Cx43 mRNA水平。Cx43 mRNA在其3′-非翻译区含有两个miR-206/miR-1结合位点，这两个位点都是有效下调所必需的。虽然之前已经证明miR-1参与肌生成，但在这项工作中，我们表明miR-206在小鼠体内围产期骨骼肌发育期间也上调，并且miR-1和miR-206在体外成肌细胞融合期间下调Cx43表达。单神经支配的肌纤维的正确发育需要肌肉收缩和NMJ末端选择，并且假设通过间隙连接的长时间电耦合可能对该过程有害。这项工作详细介绍了在肌生成过程中发生的Cx43初始下调的机制，并强调了在分化和发育过程中用于调节间隙连接的严格控制机制。
Skeletal myoblast fusion in vitro requires the expression of connexin43 (Cx43) gap junction channels. However, gap junctions are rapidly downregulated after the initiation of myoblast fusion in vitro and in vivo. In this study we show that this downregulation is accomplished by two related microRNAs, miR-206 and miR-1, that inhibit the expression of Cx43 protein during myoblast differentiation without altering Cx43 mRNA levels. Cx43 mRNA contains two binding sites for miR-206/miR-1 in its 3′-untranslated region, both of which are required for efficient downregulation. While it has been demonstrated before that miR-1 is involved in myogenesis, in this work we show that miR-206 is also upregulated during perinatal skeletal muscle development in mice in vivo and that both miR-1 and miR-206 downregulate Cx43 expression during myoblast fusion in vitro. Proper development of singly innervated muscle fibers requires muscle contraction and NMJ terminal selection and it is hypothesized that prolonged electrical coupling via gap junctions may be detrimental to this process. This work details the mechanism by which initial downregulation of Cx43 occurs during myogenesis and highlights the tight control mechanisms that are utilized for the regulation of gap junctions during differentiation and development.