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A novel protein encoded by circKANSL1L regulates skeletal myogenesis via the Akt-FoxO3 signaling axis

文献类型： 外文期刊

作者： Lin, Zekun 1 ; Xie, Fang 1 ; He, Xiao 1 ; Wang, Jing 2 ; Luo, Junyi 1 ; Chen, Ting 1 ; Jiang, Qingyan 1 ; Xi, Qianyun 1 ; Zhang, Yongliang 1 ; Sun, Jiajie 1 ;

作者机构： 1.South China Agr Univ, Coll Anim Sci, Natl Engn Res Ctr Breeding Swine Ind,State Key Lab, Guangdong Prov Key Lab Anim Nutr Control, Guangzhou 510642, Guangdong, Peoples R China

2.Henan Acad Agr Sci, Inst Anim Husb & Vet Med, Zhengzhou 450002, Peoples R China

关键词： Meat quality; Myofiber types; Single -cell sequencing; Metabolome; Ribosome profiling

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.2； 五年影响因子：7.8 ）

ISSN： 0141-8130

年卷期： 2024 年 257 卷

页码：

收录情况： SCI

摘要： 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 Riboseq, 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 trans-formation 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.

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