tRNA-derived small non-coding RNAs as novel epigenetic molecules regulating adipogenesis

tRNA-derived fragments (tRFs) are a novel class of non-coding RNA that play an vital role in regulating gene expression at post-transcriptional level. To date, it is completely unknown the regulatory mechanism of tRFs governing fat deposition and adipogenesis. In this study, we used high fat diet successfully induced obese rat model, and used tRFs transcriptome sequencing to select differentially expressed tRFs that response to obesity. We found tRFGluTTC was the highest fold change in the 296 differentially expressed tRFs, which promoted preadipocytes proliferation by increasing the expression of cell cycle regulatory factors. Moreover, tRFGluTTC also suppressed preadipocytes differentiation by reducing lipid accumulation and triglyceride content, and decreasing the expression of genes related to fatty acid synthesis. According to luciferase activity assays, tRFGluTTC directly targeted KLF9, KLF11, and KLF12, and could significantly suppressed the mRNA expression of these target genes. Besides, tRFGluTTC suppressed adipogenesis also accompanied by decreasing the expression of adipogenic transcription factors (AP2, C/EBPα, and PPARγ). Taken together, these results imply that tRFGluTTC may take as a novel epigenetic molecules governing adipogenesis and could be a target for therapeutic intervention in obesity. Adipose small mRNA profiles (15-40 nt) of high fat diet induced obesity rats and control were generated by deep sequencing, in triplicate, using Illumina Hi-Seq 2500.