College of Animal Science, Shanxi Agricultural University, Jinzhong 030801, China.
Int J Mol Sci. 2024 Nov 18;25(22):12351. doi: 10.3390/ijms252212351.
The Guangling Large-Tailed sheep is renowned for its unique tail fat deposition, with a significant proportion of its total body fat being localized in the tail region. Fat deposition is a complex biological process regulated by various molecular mechanisms. Our previous studies have identified a large number of differentially expressed circular RNAs (circRNAs) in the tail adipose tissue of the Guangling Large-Tailed sheep. These circRNAs may play a pivotal role in the process of fat deposition. Given the potential regulatory functions of circRNAs in adipose metabolism, investigating their roles in tail fat deposition is of significant scientific importance. In this study, we identified novel circARID1A. Using various experimental methods, including lentivirus infection, RNase R treatment, actinomycin D assay, qPCR, western blotting, and dual-luciferase reporter assays, we determined that circARID1A inhibits the expression of miR-493-3p through competitive binding, thereby regulating adipocyte differentiation. Further research revealed that miR-493-3p promotes adipocyte differentiation by targeting YTH domain family 2 (YTHDF2), and this regulatory effect is also influenced by circARID1A. In conclusion, our findings suggest that circARID1A inhibits tail fat cell differentiation in the Guangling Large-Tailed sheep through the circARID1A/miR-493-3p/YTHDF2 axis, providing theoretical support for improving meat quality and fat deposition in sheep.
广灵大尾羊以其独特的尾部脂肪沉积而闻名，其体内大部分脂肪都集中在尾部。脂肪沉积是一个受多种分子机制调节的复杂生物学过程。我们之前的研究已经在广灵大尾羊的尾部脂肪组织中鉴定到大量差异表达的环状 RNA（circRNA）。这些 circRNA 可能在脂肪沉积过程中发挥关键作用。鉴于 circRNA 在脂肪代谢中的潜在调节功能，研究它们在尾部脂肪沉积中的作用具有重要的科学意义。在这项研究中，我们鉴定了 novel circARID1A。通过使用慢病毒感染、RNase R 处理、放线菌素 D 测定、qPCR、western blot 和双荧光素酶报告基因检测等多种实验方法，我们确定 circARID1A 通过竞争性结合抑制 miR-493-3p 的表达，从而调控脂肪细胞分化。进一步的研究表明，miR-493-3p 通过靶向 YTH 结构域家族 2（YTHDF2）促进脂肪细胞分化，这种调节作用也受 circARID1A 的影响。总之，我们的研究结果表明，circARID1A 通过 circARID1A/miR-493-3p/YTHDF2 轴抑制广灵大尾羊尾部脂肪细胞的分化，为改善绵羊的肉质和脂肪沉积提供了理论依据。
