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.
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http://dx.doi.org/10.1111/cpr.13416 | DOI Listing |
Trends Mol Med
January 2025
Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China. Electronic address:
Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) - a protease released by skeletal muscle during PA - acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.
View Article and Find Full Text PDFJ Med Genet
January 2025
Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Biallelic pathogenic variants in cause a fatal autosomal recessive multisystem disorder characterized by recurrent autoinflammation, hypomyelination, progressive neurodegeneration, microcephaly, failure to thrive, liver dysfunction, respiratory chain defects and accumulation of glycogen in skeletal muscle. No missense variants in have been reported to date.We report a 6-year-old boy with microcephaly, global developmental delays, lower limb spasticity with hyperreflexia, epilepsy, abnormal brain MRI, failure to thrive, recurrent fevers and transaminitis.
View Article and Find Full Text PDFMol Cell Endocrinol
January 2025
Department of Physiology and Biophysics, Rush University, Chicago, United States.
The incidence and prevalence of muscular disorders and of type 2 diabetes (T2D) is increasing and both represent highly significant healthcare problems, both economically and compromising quality of life. Interestingly, skeletal muscle dysfunction and T2D share some commonalities including dysregulated glucose homeostasis, increased oxidative stress, dyslipidemia, and cytokine alterations. Several lines of evidence have hinted to a relationship between skeletal muscle dysfunction and T2D.
View Article and Find Full Text PDFAnn Nutr Metab
January 2025
Department of Translational Medical Science, University of Naples Federico II, Napoli, Italy.
Background: Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest.
Summary: Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis.
Eur J Radiol
January 2025
Jiangsu Province Nantong City Cancer Hospital, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu Province 226001, China. Electronic address:
Objective: This study aimed to explore the predictive value of baseline CT body composition and its early changes on recurrence-free survival (RFS) following radical gastrectomy, while also assessing potential sex-related differences.
Methods: We conducted a retrospective analysis of gastric cancer (GC) patients with confirmed pathology from October 2019 to May 2023. All patients underwent preoperative and postoperative CT scans to assess visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle density (SMD), along with calculating their respective rates of change.
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