Profiling and Functional Analysis of Circular RNAs in Porcine Fast and Slow Muscles
Profiling and Functional Analysis of Circular RNAs in Porcine Fast and Slow Muscles
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DOI：
10.3389/fcell.2020.00322
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发表时间：
2020-05-26
影响因子：
5.5
通讯作者：
Wu, Wangjun
中科院分区：
文献类型：
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作者：
Li, Bojiang;Yin, Di;Wu, Wangjun
不同的骨骼肌纤维类型表现出明显不同的生理和代谢特性，并与人类代谢疾病和牲畜肉质性状有关。环状RNA（circular RNA，circRNA）是一类新的内源性基因表达调控RNA，但其对骨骼肌纤维的调控机制尚不清楚。在这里，我们使用RNA-seq构建了猪的三个快收缩股二头肌（Bf）和三个慢收缩比目鱼肌（Sol）的circRNA表达谱，并确定了16，342个不同的circRNA候选者。值得注意的是，在Bf和Sol肌肉之间鉴定了242种差异表达（DE）的circRNA，包括105种上调和137种下调的circRNA，因此它们是调节骨骼肌纤维转化的潜在候选者。此外，DE circRNA的宿主基因的基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径富集分析揭示，宿主基因主要涉及骨骼肌纤维相关GO术语（例如，肌肉收缩、收缩纤维部分和Z盘）和骨骼肌纤维相关的信号传导途径（例如，AMPK和cGMP-PKG）。我们还使用先前获得的高通量测序mRNA和miRNA数据构建了DE circRNA-miRNA-mRNA的共表达网络，从中鉴定了112种circRNA-miRNA和95种miRNA-mRNA相互作用。多个circRNA基本上充当miR-499 - 5p的海绵，miR-499 - 5p优先在慢缩肌中表达并降低杜氏肌营养不良症（DMD）的严重程度。综上所述，鉴定了一系列参与猪骨骼肌生长和发育的新型候选circRNA。此外，它们为进一步深入研究circRNA在骨骼肌纤维形成中的调控机制提供了全面的circRNA资源，并可能为人类骨骼肌疾病提供见解。
The different skeletal muscle fiber types exhibit distinctively different physiological and metabolic properties, and have been linked to both human metabolic diseases and meat quality traits in livestock. Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression, but regulatory mechanisms of skeletal muscle fibers involved in circRNAs remain poorly understood. Here, we constructed circRNA expression profiles of three fast-twitch biceps femoris (Bf) and three slow-twitch soleus (Sol) muscles in pigs using RNA-seq and identified 16,342 distinct circRNA candidates. Notably, 242 differentially expressed (DE) circRNAs between Bf and Sol muscles were identified, including 105 upregulated and 137 downregulated circRNAs, and are thus potential candidates for the regulation of skeletal muscle fiber conversion. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of host genes of DE circRNAs revealed that host genes were mainly involved in skeletal muscle fiber-related GO terms (e.g., muscle contraction, contractile fiber part, and Z disk) and skeletal muscle fiber-related signaling pathways (e.g., AMPK and cGMP-PKG). We also constructed co-expression networks of DE circRNA-miRNA-mRNA using previously acquired high-throughput sequencing mRNA and miRNA data, from which 112 circRNA-miRNA and 95 miRNA-mRNA interactions were identified. Multiple circRNAs essentially serve as a sponge for miR-499-5p, which is preferentially expressed in slow-twitch muscle and reduces the severity of Duchenne muscular dystrophy (DMD). Taken together, a series of novel candidate circRNAs involved in the growth and development of porcine skeletal muscle was identified. Furthermore, they provide a comprehensive circRNA resource for further in-depth research on the regulatory mechanisms of circRNA in the formation of skeletal muscle fiber, and may provide insights into human skeletal muscle diseases.