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牛增强子调控的 circSGCB 通过增强 KLF3 表达作为 ceRNA 调控骨骼肌发育。

Bovine enhancer-regulated circSGCB acts as a ceRNA to regulate skeletal muscle development via enhancing KLF3 expression.

机构信息

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.

Qinghai Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining 810016, China.

出版信息

Int J Biol Macromol. 2024 Mar;261(Pt 2):129779. doi: 10.1016/j.ijbiomac.2024.129779. Epub 2024 Jan 28.

Abstract

Skeletal muscle growth and development in livestock and poultry play a pivotal role in determining the quality and yield of meat production. However, the mechanisms of myogenesis are remained unclear due to it finely regulated by a complex network of biological macromolecules. In this study, leveraging previous sequencing data, we investigated a differentially expressed circular RNA (circSGCB) present in fetal and adult muscle tissues among various ruminant species, including cattle, goat, and sheep. Our analysis revealed that circSGCB is a single exon circRNA, potentially regulated by an adjacent bovine enhancer. Functional analysis through loss-of-function tests demonstrated that circSGCB exerts inhibitory effects on bovine myoblast proliferation while promoting myocytes generation. Furthermore, we discovered that circSGCB primarily localizes to the cytoplasm, where it functions as a molecular sponge by binding to bta-miR-27a-3p. This interaction releases the mRNAs of KLF3 gene and further activates downstream functional pathways. In vivo, studies provided evidence that up-regulation of KLF3 contributes to muscle regeneration. These findings collectively suggest that circSGCB operates via a competing endogenous RNA (ceRNA) mechanism to regulate KLF3, thereby influencing myogenesis in ruminants and highlights it may as potential molecular targets for enhancing meat production in livestock and poultry industries.

摘要

骨骼肌在牲畜和家禽的生长和发育中起着关键作用,决定了肉产量的质量和产量。然而,由于它受生物大分子的复杂网络精细调节,肌发生的机制仍不清楚。在这项研究中,我们利用以前的测序数据,研究了不同反刍动物(包括牛、山羊和绵羊)的胎儿和成年肌肉组织中存在的差异表达环状 RNA (circSGCB)。我们的分析表明,circSGCB 是一种单外显子环状 RNA,可能受邻近牛增强子的调控。通过功能丧失测试进行的功能分析表明,circSGCB 对牛成肌细胞增殖具有抑制作用,同时促进肌细胞生成。此外,我们发现 circSGCB 主要定位于细胞质,在那里它作为分子海绵通过与 bta-miR-27a-3p 结合发挥作用。这种相互作用释放 KLF3 基因的 mRNA,并进一步激活下游功能途径。在体内,研究提供了证据表明 KLF3 的上调有助于肌肉再生。这些发现共同表明,circSGCB 通过竞争性内源性 RNA (ceRNA) 机制来调节 KLF3,从而影响反刍动物的肌发生,并突出其可能作为提高家畜和家禽产业肉产量的潜在分子靶标。

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