College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Biomolecules. 2019 Jul 11;9(7):274. doi: 10.3390/biom9070274.
tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high fat diet was employed to induce an obese rat model, and tRFs transcriptome sequencing was conducted to identify differentially expressed tRFs that response to obesity. We found out that tRF, which promoted preadipocyte proliferation by increasing expressions of cell cycle regulatory factors, had the highest fold change in the 296 differentially expressed tRFs. Moreover, tRF also suppressed preadipocyte differentiation by reducing triglyceride content and lipid accumulation, and by decreasing expressions of genes that related to fatty acid synthesis. According to results of luciferase activity analysis, tRF directly targeted Kruppel-like factor (KLF) 9, KLF11, and KLF12, thus significantly suppressing mRNA expressions of these target genes. Moreover, tRF suppressed adipogenesis, accompanying by suppressing expressions of adipogenic transcription factors (, , and ). In conclusion, these results imply that tRF may act as a novel epigenetic molecule regulating adipogenesis and could provide a new strategy for the intervention treatment of obesity.
tRNA 衍生的小片段（tRFs）是一类新型的非编码 RNA，来源于 tRNA，在转录后水平调控基因表达中发挥重要作用。迄今为止，tRFs 调控脂肪沉积和脂肪生成的调控机制尚不清楚。在本研究中，我们采用高脂肪饮食诱导肥胖大鼠模型，并进行 tRFs 转录组测序，以鉴定响应肥胖的差异表达 tRFs。我们发现，通过增加细胞周期调控因子的表达促进前体脂肪细胞增殖的 tRF，在 296 个差异表达的 tRFs 中具有最高的倍数变化。此外，tRF 还通过降低甘油三酯含量和脂质积累，以及降低与脂肪酸合成相关的基因表达，抑制前体脂肪细胞分化。根据荧光素酶活性分析的结果，tRF 直接靶向 Kruppel 样因子（KLF）9、KLF11 和 KLF12，从而显著抑制这些靶基因的 mRNA 表达。此外，tRF 抑制脂肪生成，同时抑制脂肪生成转录因子（、和）的表达。总之，这些结果表明 tRF 可能作为一种新型的表观遗传分子调节脂肪生成，并为肥胖的干预治疗提供新策略。
