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环状 RNA circ003429 通过与 miR-199a-3p 相互作用,靶向基因调控奶山羊乳腺不饱和脂肪酸的合成。

Circ003429 Regulates Unsaturated Fatty Acid Synthesis in the Dairy Goat Mammary Gland by Interacting with miR-199a-3p, Targeting the Gene.

机构信息

College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China.

Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

出版信息

Int J Mol Sci. 2022 Apr 6;23(7):4068. doi: 10.3390/ijms23074068.

Abstract

Fatty acid composition is a key factor affecting the flavor and quality of goat milk. CircRNAs are now recognized as important regulators of transcription, and they play an important role in the control of fatty acid synthesis. Thus, understanding the regulatory mechanisms controlling this process in ruminant mammary glands is of great significance. In the present study, mammary tissue from dairy goats during early lactation and the dry period (nonlactating) were collected and used for high-throughput sequencing. Compared to levels during the dry period, the expression level of circ003429 during early lactation was lower (12.68-fold downregulated). In isolated goat mammary epithelial cells, circ003429 inhibited the synthesis of triglycerides (TAG) and decreased the content of unsaturated fatty acids (C16:1, C18:1, and C18:2), indicating that this circRNA plays an important role in regulating lipid synthesis. A binding site for miR-199a-3p in the circ003429 sequence was detected, and a dual-luciferase reporter system revealed that circ003429 targets miR-199a-3p. Overexpression of circ003429 (pcDNA-circ003429) downregulated the abundance of miR-199a-3p. In contrast, overexpression of miR-199a-3p increased TAG content and decreased mRNA abundance of Yes-associated protein 1 () (a target gene of miR-199a-3p), and TAG content was decreased and mRNA abundance was increased in response to overexpression of circ003429. These results indicate that circ003429 alleviates the inhibitory effect of miR-199a-3p on the mRNA abundance of by binding miR-199a-3p, resulting in subsequent regulation of the synthesis of TAG and unsaturated fatty acids.

摘要

脂肪酸组成是影响羊奶风味和品质的关键因素。circRNAs 现在被认为是转录的重要调节剂,它们在控制脂肪酸合成中起着重要作用。因此,了解控制反刍动物乳腺中这一过程的调节机制具有重要意义。本研究采集了泌乳早期和干乳期(非泌乳期)奶山羊的乳腺组织进行高通量测序。与干乳期相比,泌乳早期 circ003429 的表达水平较低(下调 12.68 倍)。在分离的山羊乳腺上皮细胞中,circ003429 抑制甘油三酯(TAG)的合成,并降低不饱和脂肪酸(C16:1、C18:1 和 C18:2)的含量,表明该 circRNA 在调节脂质合成中发挥重要作用。在 circ003429 序列中检测到 miR-199a-3p 的结合位点,双荧光素酶报告系统显示 circ003429 靶向 miR-199a-3p。circ003429 的过表达(pcDNA-circ003429)降低了 miR-199a-3p 的丰度。相反,miR-199a-3p 的过表达增加了 TAG 含量并降低了 Yes 相关蛋白 1 ()(miR-199a-3p 的靶基因)的 mRNA 丰度,而过表达 circ003429 则降低了 TAG 含量并增加了其 mRNA 丰度。这些结果表明,circ003429 通过结合 miR-199a-3p 减轻了 miR-199a-3p 对 mRNA 丰度的抑制作用,从而随后调节 TAG 和不饱和脂肪酸的合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c195/8999533/61cf9348c5ec/ijms-23-04068-g001.jpg

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