Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) modulate gene expression programs in physiology and disease. Here, we report a noncoding RNA regulatory network that modulates myoblast fusion into multinucleated myotubes, a process that occurs during muscle development and muscle regeneration after injury. In early stages of human myogenesis, the levels of lncRNA OIP5-AS1 increased, while the levels of miR-7 decreased. Moreover, OIP5-AS1 bound and induced miR-7 decay via target RNA-directed miRNA decay; accordingly, loss of OIP5-AS1 attenuated, while antagonizing miR-7 accelerated, myotube formation. We found that the OIP5-AS1-mediated miR-7 degradation promoted myoblast fusion, as it derepressed the miR-7 target MYMX mRNA, which encodes the fusogenic protein myomixer (MYMX). Remarkably, an oligonucleotide site blocker interfered with the OIP5-AS1-directed miR-7 degradation, allowing miR-7 to accumulate, lowering MYMX production and suppressing myotube formation. These results highlight a mechanism whereby lncRNA OIP5-AS1-mediated miR-7 decay promotes myotube formation by stimulating a myogenic fusion program.

中文翻译：

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LncRNA OIP5-AS1 定向的 miR-7 降解促进人肌生成过程中 MYMX 的产生

长链非编码 RNA (lncRNA) 和 microRNA (miRNA) 在生理学和疾病中调节基因表达程序。在这里，我们报告了一个非编码 RNA 调节网络，该网络调节成肌细胞融合成多核肌管，这一过程发生在肌肉发育和受伤后的肌肉再生过程中。在人类肌生成的早期阶段，lncRNA OIP5-AS1 水平升高，而 miR-7 水平降低。此外，OIP5-AS1 通过目标 RNA 定向的 miRNA 衰变结合并诱导 miR-7 衰变；因此，OIP5-AS1 的损失减弱，同时拮抗 miR-7 加速了肌管形成。我们发现 OIP5-AS1 介导的 miR-7 降解促进了成肌细胞融合，因为它解除了 miR-7 靶标 MYMX mRNA 的抑制，该 mRNA 编码融合蛋白 myomixer (MYMX)。值得注意的是，寡核苷酸位点阻断剂干扰 OIP5-AS1 定向的 miR-7 降解，使 miR-7 积累，降低 MYMX 产生并抑制肌管形成。这些结果突出了 lncRNA OIP5-AS1 介导的 miR-7 衰变通过刺激生肌融合程序促进肌管形成的机制。