Adenosine-to-inosine (A-to-I) RNA editing meditated by adenosine deaminases acting on RNA (ADARs) enzymes is a widespread post-transcriptional event in mammals. However, A-to-I editing in skeletal muscle remains poorly understood. By integrating strand-specific RNA-seq, whole genome bisulphite sequencing, and genome sequencing data, we comprehensively profiled the A-to-I editome in developing skeletal muscles across 27 prenatal and postnatal stages in pig, an important farm animal and biomedical model. We detected 198,892 A-to-I editing sites and found that they occurred more frequently at prenatal stages and showed low conservation among pig, human, and mouse. Both the editing level and frequency decreased during development and were positively correlated with ADAR enzymes expression. The hyper-edited genes were functionally related to the cell cycle and cell division. A co-editing module associated with myogenesis was identified. The developmentally differential editing sites were functionally enriched in genes associated with muscle development, their editing levels were highly correlated with expression of their host mRNAs, and they potentially influenced the gain/loss of miRNA binding sites. Finally, we developed a database to visualize the Sus scrofa RNA editome. Our study presents the first profile of the dynamic A-to-I editome in developing animal skeletal muscle and provides evidences that RNA editing is a vital regulator of myogenesis.

中文翻译：

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Suscrofa骨骼肌中RNA编辑组的发育图谱。

在哺乳动物中，由作用于RNA（ADARs）的腺苷脱氨基酶介导的腺苷-肌苷（A-I）RNA编辑是一个广泛的转录后事件。但是，骨骼肌的A-to-I编辑仍然知之甚少。通过整合链特异性RNA-seq，全基因组亚硫酸氢盐测序和基因组测序数据，我们对猪的27个产前和产后阶段骨骼肌的发育过程中的A-to-I编辑组进行了全面分析，这是重要的农场动物和生物医学模型。我们检测到198,892个从A到I的编辑位点，发现它们在产前阶段的发生频率更高，并且在猪，人和小鼠中显示出较低的保守性。在开发过程中，编辑水平和频率均降低，并且与ADAR酶表达呈正相关。过度编辑的基因在功能上与细胞周期和细胞分裂有关。确定了与肌发生相关的共同编辑模块。发育差异的编辑位点在功能上丰富了与肌肉发育相关的基因，它们的编辑水平与宿主mRNA的表达高度相关，并且它们潜在地影响了miRNA结合位点的增减。最后，我们开发了一个数据库来可视化Sus scrofa RNA编辑组。我们的研究提出了动态A-to-I编辑组在发育中的动物骨骼肌中的第一个特征，并提供了RNA编辑是肌发生的重要调节剂的证据。发育差异的编辑位点在功能上丰富了与肌肉发育相关的基因，它们的编辑水平与宿主mRNA的表达高度相关，并且它们潜在地影响了miRNA结合位点的增减。最后，我们开发了一个数据库来可视化Sus scrofa RNA编辑组。我们的研究提出了动态A-to-I编辑组在发育中的动物骨骼肌中的第一个特征，并提供了RNA编辑是肌发生的重要调节剂的证据。发育差异的编辑位点在功能上丰富了与肌肉发育相关的基因，它们的编辑水平与宿主mRNA的表达高度相关，并且它们潜在地影响了miRNA结合位点的增减。最后，我们开发了一个数据库来可视化Sus scrofa RNA编辑组。我们的研究提出了动态A-to-I编辑组在发育中的动物骨骼肌中的第一个特征，并提供了RNA编辑是肌发生的重要调节剂的证据。