mt-Ty 5´tiRNA regulates skeletal muscle cell proliferation and differentiation.
Jun CaoXin WangVivek AdvaniYao Wei LuAndrea P MaliziaGurinder Bir SinghZhan-Peng HuangJianming LiuChunbo WangEdilamar M OliveiraJohn D MablyKaifu ChenDa-Zhi WangPublished in: Cell proliferation (2023)
In this study, we sought to determine the role of tRNA-derived fragments in the regulation of gene expression during skeletal muscle cell proliferation and differentiation. We employed cell culture to examine the function of mt-Ty 5' tiRNAs. Northern blotting, RT-PCR as well as RNA-Seq, were performed to determine the effects of mt-Ty 5' tiRNA loss and gain on gene expression. Standard and transmission electron microscopy (TEM) were used to characterize cell and sub-cellular structures. mt-Ty 5'tiRNAs were found to be enriched in mouse skeletal muscle, showing increased levels in later developmental stages. Gapmer-mediated inhibition of tiRNAs in skeletal muscle C2C12 myoblasts resulted in decreased cell proliferation and myogenic differentiation; consistent with this observation, RNA-Seq, transcriptome analyses, and RT-PCR revealed that skeletal muscle cell differentiation and cell proliferation pathways were also downregulated. Conversely, overexpression of mt-Ty 5'tiRNAs in C2C12 cells led to a reversal of these transcriptional trends. These data reveal that mt-Ty 5'tiRNAs are enriched in skeletal muscle and play an important role in myoblast proliferation and differentiation. Our study also highlights the potential for the development of tiRNAs as novel therapeutic targets for muscle-related diseases.
Keyphrases
- skeletal muscle
- rna seq
- single cell
- cell proliferation
- gene expression
- insulin resistance
- cell cycle
- dna methylation
- transcription factor
- electron microscopy
- signaling pathway
- type diabetes
- pi k akt
- genome wide
- stem cells
- machine learning
- cell cycle arrest
- metabolic syndrome
- oxidative stress
- high resolution
- cell death
- cell therapy
- drug induced
- data analysis
- mass spectrometry