A novel tsRNA-16902 regulating the adipogenic differentiation of human bone marrow mesenchymal stem cells

Abstract

Background: Transfer RNA-derived small RNAs (tsRNAs) are a recently discovered form of non-coding RNA capable of regulating myriad physiological processes. The role of tsRNAs in hMSC adipogenic differentiation, however, remains incompletely understood. The purpose of this study was to identify the novel tsRNA-16902 as a regulator of hMSC adipogenic differentiation. Methods: In this study, we conducted transcriptomic sequencing of hMSCs after inducing their adipogenic differentiation, and we were thereby able to clarify the molecular mechanism underlying the role of tsRNA-16902 in this context via a series of molecular biology methods. Results: When we knocked down tsRNA-16902 expression, this impaired hMSC adipogenic differentiation and associated marker gene expression. Bioinformatics analyses further revealed tsRNA-16902 to target retinoic acid receptor γ (RARγ). Luciferase reporter assays also confirmed the ability of tsRNA-16902 to bind to the RARγ 3′untranslated region. Consistent with this, RARγ overexpression led to impaired hMSC adipogenesis. Further analyses revealed that Smad2/3 phosphorylation was increased in cells that either overexpressed RARγ or in which tsRNA-16902 had been knocked down. We also assessed the adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down and at the same time a Smad2/3 inhibitor was added to disrupt Smad2/3 phosphorylation. The adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down was further enhanced upon the addition of a Smad2/3 signaling inhibitor relative to tsRNA-16902 knockdown alone. Conclusions: Through a comprehensive profiling analysis of tsRNAs that were differentially expressed in the context of hMSC adipogenic differentiation, we were able to identify tsRNA-16902 as a previously uncharacterized regulator of adipogenesis. tsRNA-16902 is able to regulate hMSC adipogenic differentiation by targeting RARγ via the Smad2/3 signaling pathway. Together, our results may thus highlight novel strategies of value for treating obesity.

A Novel tiRNA-Gly-GCC-1 Promotes Progression of Urothelial Bladder Carcinoma and Directly Targets TLR4

“…For instance, tRFs derived from tRNALysCTT and tRNAPheGAA were found to act as a good indicator of progression-free survival and a candidate prognostic marker in prostate cancer [ 17 ]. It was reported that tsRNA-16902 was able to regμLate hMSC adipogenic differentiation by targeting RARγ via the Smad2/3 signaling pathway [ 18 ]. In clear cell renal cell carcinoma, 5′-tRNA-Arg-CCT, 5′-tRNA-Glu-CTC, and 5′-tRNA-Lys-TTT halves were circμLating at lower levels in serum samples of patients, indicating a potential role as a tumor suppressor [ 19 ].…”

The effect of narcotics on ferroptosis-related molecular mechanisms and signalling pathways

“…Additionally, in SGC7901 gastric cancer cells, levobupivacaine treatment elevated the level of miR-489-3p and further acted as a sponge for SLC7A11 to inhibit its expression, thereby promoting ferroptosis in gastric cancer cells ( Mao et al, 2021 ). Transfer RNA‐derived small RNAs (tsRNAs) are an abundant type of noncoding small RNAs that play multiple roles in different physiological processes ( Kim et al, 2017 ; Wang et al, 2020c ). There is increasing evidence that tsRNA is capable of affecting gene expression at the posttranscriptional level by targeting the 3′UTR, showing a mechanism similar to that of miRNAs ( Canella et al, 2010 ; Haussecker et al, 2010 ).…”

Paternal High-Fat Diet Altered Sperm 5'tsRNA-Gly-GCC Is Associated With Enhanced Gluconeogenesis in the Offspring

“…The improved sequencing platform and methods have recently made us realize that mature tRNAs can also produce sncRNA molecules via site specific cleavage by various RNase, such as angiogenin (ANG) and Dicer ( Sun et al, 2018 ). These tRNA-derived small RNAs (tsRNAs), also known as tRNA fragments (tRFs), could participate in translation inhibition and play a regulatory role in a variety of physiological and pathological phenomena ( Sun et al, 2018 ), and have also attracted progressively more attention in epigenetic research field recently ( Gebetsberger and Polacek, 2013 ; Keam and Hutvagner, 2015 ; Wang et al, 2020b ; Rashad et al, 2020 ).…”

“…More and more studies have found that tsRNAs play an important role in metabolic disorders ( Chen et al, 2016 ; Wang et al, 2020a ; Wang et al, 2020b ). Mouse mature sperm contains a large amount of tsRNA, which is much higher than miRNA and piRNA ( Peng et al, 2012 ).…”