State Key Laboratory of Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China.
Key laboratory of yak Breeding Engineering Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
Genes (Basel). 2020 Apr 10;11(4):414. doi: 10.3390/genes11040414.
The yak ( grunniens) is subjected to nutritional deficiency during the whole winter grazing season; deciphering the adipose metabolism and energy homeostasis under cold and nutrients stress conditions could be a novel way to understand the specific mechanism of energy metabolism. Circular RNAs (circRNAs) have elucidated that they play a key role in many biological events, but the regulatory function of adipose development remains mostly unknown. Therefore, the expression pattern of circRNAs were identified for the first time during yak adipocyte differentiation to gain insight into their potential functional involvement in bovine adipogenesis. We detected 7203 circRNA candidates, most of them contained at least two exons, and multiple circRNA isoforms could be generated from one parental gene. Analysis of differential expression circRNAs displayed that 136 circRNAs were differentially expressed at day 12 (Ad) after adipocyte differentiation, compared with the control at day 0 (Pread 0), while 7 circRNAs were detected on day 2. Sanger sequencing validated that six circRNAs had head-to-tail junction, and quantitative real-time PCR (qPCR) results revealed that the expression patterns of ten circRNAs were consistent with their expression levels from RNA-sequencing (RNA-seq) data. We further predicted the networks of circRNA-miRNA-gene based on miRNAs sponging by circRNAs, in which genes were participated in the adipocyte differentiation-related signaling pathways. After that, we constructed several adipocyte differentiation-related ceRNAs and revealed six circRNAs (novel_circ_0009127, novel_circ_0000628, novel_circ_0011513, novel_circ_0010775, novel_circ_0006981 and novel_circ_0001494) were related to adipogenesis. Furthermore, we analyzed the homology among yak, human and mouse circRNAs and found that 3536 yak circRNAs were homologous to human and mouse circRNAs. In conclusion, these findings provide a solid basis for the investigation of yak adipocyte differentiation-related circRNAs and serve as a great reference to study the energy metabolism of high-altitude animals.
牦牛在整个冬季放牧季节都受到营养缺乏的影响；在寒冷和营养压力条件下破译脂肪代谢和能量稳态可以是了解能量代谢特定机制的一种新方法。环状 RNA（circRNA）已被阐明在许多生物事件中发挥关键作用，但脂肪发育的调节功能在很大程度上仍然未知。因此，首次在牦牛脂肪细胞分化过程中鉴定了 circRNA 的表达模式，以深入了解它们在牛脂肪生成中的潜在功能。我们检测到 7203 个 circRNA 候选者，其中大多数至少包含两个外显子，并且一个亲本基因可以产生多个 circRNA 同种型。差异表达 circRNA 的分析显示，与分化前 0 天（Pread 0）相比，在脂肪细胞分化 12 天后（Ad）有 136 个 circRNA 差异表达，而在第 2 天检测到 7 个 circRNA。Sanger 测序验证了 6 个 circRNA 具有头到尾连接，定量实时 PCR（qPCR）结果显示 10 个 circRNA 的表达模式与其 RNA 测序（RNA-seq）数据的表达水平一致。我们进一步基于 circRNA 对 miRNA 的海绵作用预测了 circRNA-miRNA-gene 的网络，其中基因参与了脂肪细胞分化相关的信号通路。之后，我们构建了几个与脂肪细胞分化相关的 ceRNA，并揭示了 6 个 circRNA（novel_circ_0009127、novel_circ_0000628、novel_circ_0011513、novel_circ_0010775、novel_circ_0006981 和 novel_circ_0001494）与脂肪生成有关。此外，我们分析了牦牛、人和小鼠 circRNA 之间的同源性，发现 3536 个牦牛 circRNA 与人和小鼠 circRNA 同源。总之，这些发现为研究牦牛脂肪细胞分化相关 circRNA 提供了坚实的基础，并为研究高原动物的能量代谢提供了很好的参考。
