Abstract：
Skeletal muscle is one the largest organs of the body and is involved in animal production and human health. Circular RNAs (circRNAs) have been implicated in skeletal myogenesis through largely unknown mechanisms. Herein, we report the phenotypic and metabolomic analysis of porcine longissimus dorsi muscles in Lantang and Landrace piglets, revealing a high-content of slow-oxidative fibers responsible for high-quality meat product in Lantang piglets. Using single-cell transcriptomics, we identified four myogenesis-related cell types, and the Akt-FoxO3 signaling axis was the most significantly enriched pathway in each subpopulation in the different pig breeds, as well as in fast-twitch glycolytic fibers. Using the multi-dimensional bioinformatic tools of circRNAome-seq and Ribo-seq, we identified a novel circRNA, circKANSL1L, with a protein-coding ability in porcine muscles, whose expression level correlated with myoblast proliferation and differentiation in vitro, as well as the transformation between distinct mature myofibers in vivo. The protein product of circKANSL1L could interact with Akt to decrease the phosphorylation level of FoxO3, which subsequently promoted FoxO3 transcriptional activity to regulate skeletal myogenesis. Our results established the existence of a protein encoded by circKANSL1L and demonstrated its potential functions in myogenesis.
摘要：
骨骼肌是人体最大的器官之一，参与动物生产和人类健康。环状RNA(circularRNAs,circRNAs)已经通过很大程度上未知的机制与骨骼肌发生有关。在这里，我们报道了蓝塘和长白猪的猪背最长肌的表型和代谢组学分析，揭示了高含量的慢氧化纤维，负责蓝塘仔猪的高品质肉制品。使用单细胞转录组学，我们确定了四种与肌生成相关的细胞类型，Akt-FoxO3信号轴是不同猪品种各亚群中最显著的富集途径,以及快速抽搐的糖酵解纤维。使用circRNAome-seq和Ribo-seq的多维生物信息学工具，我们发现了一种新的circRNA,大约KANSL1L,在猪肌肉中具有蛋白质编码能力，其表达水平与成肌细胞体外增殖和分化相关,以及体内不同成熟肌纤维之间的转化。circKANSL1L的蛋白质产物可以与Akt相互作用以降低FoxO3的磷酸化水平，从而促进FoxO3的转录活性以调节骨骼肌的发生。我们的结果确定了circKANSL1L编码的蛋白质的存在，并证明了其在肌生成中的潜在功能。
