Long non-coding RNA Tug1 modulates mitochondrial and myogenic responses to exercise in skeletal muscle
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ABSTRACT:
PROVIDER: PRJNA769441 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR16242500_1.fastq.gz | Fastqsanger.gz | |||
| SRR16242500_2.fastq.gz | Fastqsanger.gz | |||
| SRR16242501_1.fastq.gz | Fastqsanger.gz | |||
| SRR16242501_2.fastq.gz | Fastqsanger.gz | |||
| SRR16242502_1.fastq.gz | Fastqsanger.gz |
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Project description:Mitochondrial adaptations play a central role in the beneficial effects of exercise, particularly in metabolically active tissues such as skeletal muscle. Despite this, the molecular regulators of mitochondrial adaptive responses have not yet been fully elucidated. The long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) interacts with the master transcriptional regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In skeletal muscle of young healthy humans (n=14), we observed that TUG1 gene expression was elevated following an acute bout of continuous, moderate intensity cycling exercise and this positively correlated with PPARGC1A gene expression. Therefore, we hypothesised that TUG1 may modulate skeletal muscle mitochondrial responses to exercise. Knockdown (KD) of Tug1 in differentiating mouse myotubes resulted in altered mitochondrial morphology and impaired mitochondrial respiratory function, which was accompanied by greater myosin heavy chain slow isoform protein expression, despite lower Ppargc1a gene and MFN2 protein expression. Tug1 KD prevented the induction of Ppargc1a expression from a Ca2+ mediated stimulus (caffeine) yet the response to an AMPK agonist (AICAR ) was unaffected. RNA-sequencing revealed that Tug1 KD affected genes relating to mitochondrial Ca2+ transport and downstream targets of PGC-1α. Finally, in response to electrical pulse stimulation (EPS), an in vitro model of exercise in myotubes, there were ~300 genes whose upregulation in response to EPS was either blunted or augmented by Tug1 KD, including regulators of muscle differentiation and myogenesis. These data demonstrate that the lncRNA Tug1 is a novel regulator of skeletal muscle transcriptional responses to exercise and myogenesis.
2022-06-29 | GSE185530 | GEO
Project description:BackgroundMitochondria have an essential role in regulating metabolism and integrate environmental and physiological signals to affect processes such as cellular bioenergetics and response to stress. In the metabolically active skeletal muscle, mitochondrial biogenesis is one important component contributing to a broad set of mitochondrial adaptations occurring in response to signals, which converge on the biogenesis transcriptional regulator peroxisome proliferator-activated receptor coactivator 1-alpha (PGC-1α), and is central to the beneficial effects of exercise in skeletal muscle. We investigated the role of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1), which interacts with PGC-1α in regulating transcriptional responses to exercise in skeletal muscle.ResultsIn human skeletal muscle, TUG1 gene expression was upregulated post-exercise and was also positively correlated with the increase in PGC-1α gene expression (PPARGC1A). Tug1 knockdown (KD) in differentiating mouse myotubes led to decreased Ppargc1a gene expression, impaired mitochondrial respiration and morphology, and enhanced myosin heavy chain slow isoform protein expression. In response to a Ca2+-mediated stimulus, Tug1 KD prevented an increase in Ppargc1a expression. RNA sequencing revealed that Tug1 KD impacted mitochondrial Ca2+ transport genes and several downstream PGC-1α targets. Finally, Tug1 KD modulated the expression of ~300 genes that were upregulated in response to an in vitro model of exercise in myotubes, including genes involved in regulating myogenesis.ConclusionsWe found that TUG1 is upregulated in human skeletal muscle after a single session of exercise, and mechanistically, Tug1 regulates transcriptional networks associated with mitochondrial calcium handling, muscle differentiation and myogenesis. These data demonstrate that lncRNA Tug1 exerts regulation over fundamental aspects of skeletal muscle biology and response to exercise stimuli.
| S-EPMC9295458 | biostudies-literature
Project description:Cardiomyocyte Ca2+ is buffered by mitochondria via the mitochondrial calcium uniporter (MCU) complex. The MCU complex consists of pore-forming proteins including the mitochondrial calcium uniporter (MCU), and regulatory proteins such as mitochondrial calcium uptake proteins 1 and 2 (MICU1/2). The stoichiometry of these proteins influences the sensitivity to Ca2+ and activity of the complex. However, the factors that regulate their gene expression remain incompletely understood. Long non-coding RNAs (lncRNAs) regulate gene expression through various mechanisms, and we recently found that the lncRNA Tug1 affected the expression of MCU-associated genes. To further explore this, we knocked down Tug1 (Tug1 KD) in H9c2 rat cardiomyocytes using antisense LNA oligo. This led to increased MCU protein expression yet this did not enhance a marker of mitochondrial Ca2+ uptake. RNA-seq revealed that Tug1 KD increased Mcu and led to differential expression of genes and pathways related to Ca2+ regulation in the heart. To understand the effect of this on Ca2+ signalling, we measured phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and its downstream target cAMP Response Element-Binding protein (CREB), a transcription factor known to promote Mcu gene expression. Tug1 KD attenuated the increase in CAMKII and CREB phosphorylation in response to ionomycin, a Ca2+ ionophore. Inhibition of CaMKII, but not CREB, partially prevented the Tug1 KD mediated increase in Mcu. Together, these data suggest that Tug1 modulates MCU expression via a mechanism that may involve CAMKII and CREB. The Tug1 mediated regulation of MCU on mitochondrial Ca2+ uptake, may have functional consequences for cellular Ca2+ handling which could have implications for cardiac disease.
2023-07-22 | GSE237787 | GEO
Project description:The evolutionary conserved Taurine Upregulated Gene 1 (TUG1) is a ubiquitously expressed gene that is one of the highest expressed genes in human and rodent endothelial cells (ECs). We here show that TUG1 expression decreases significantly in aging mouse carotid artery ECs and human ECs in vitro, indicating a potential role in the aging endothelial vasculature system. We therefore investigated if, and how, TUG1 might function in aging ECs, but despite extensive phenotyping found no alterations in basal EC proliferation, apoptosis, barrier function, migration, mitochondrial function, or monocyte adhesion upon TUG1 silencing in vitro. TUG1 knockdown did slightly and significantly decrease cumulative sprout length upon vascular endothelial growth factor A stimulation in human umbilical vein endothelial cells (HUVECs), though TUG1-silenced HUVECs displayed no transcriptome-wide mRNA expression changes explaining this effect. Further, ectopic expression of the highly conserved and recently discovered 153 amino acid protein translated from certain TUG1 transcript isoforms did not alter angiogenic sprouting in vitro. Our data show that, despite a high expression and strong evolutionary conservation of both the TUG1 locus and the protein sequence it encodes, TUG1 does not seem to play a major role in basic endothelial cell function.
2022-07-20 | GSE200766 | GEO
Project description:Glioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be originated by the glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. We found TUG1, a large non-coding RNA (lncRNA) is highly expressed in GSCs. TUG1 was reported to interact with PRC2 via its exon 2 and represses its target gene expression in trans. In order to identify the genetic loci enriched with TUG1 in GSC, we performed modified RNA pull-down assay coupled with promoter-microarray analysis using BrU-labeled TUG1.
2016-11-23 | GSE65910 | GEO
Project description:Habitual exercise modulates the composition of the intestinal microbiota. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet-fed mice. The recipient mice that received fecal samples from trained donor mice for 1 week showed elevated levels of metabolic signalings in skeletal muscle. Glucose tolerance was improved by fecal microbiota transplantation after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvement in mice. We performed a microarray analysis to compare the metabolic gene expression profiles in the skeletal muscle from each mouse.
2022-06-30 | GSE201202 | GEO
Project description:We have sequenced mouse embryonic fibroblasts (MEFs) and 6 organs (testes, prostate, liver, heart, spleen, and eye) harvested from adult male wild type and Tug1 knockout (Tug1_tm1.1Vlcg) mice in a C57BL/6J/129S6 (N3-C57BL/6J, no Neo) background. Additional sequencing was done on the testes of a Tug1 rescue mouse, which contains a doxycycline inducible allele for Tug1 (tg(Tug1)) and CAGs-rtTA3 in the Tug1 knockout background (Tug1_tmn1.1Vlcg).
2020-05-27 | GSE124745 | GEO
Project description:Changes and plasticity in both gene expression and protein signaling in skeletal muscle is considered to be a major cause of metabolic syndrome, while it has been shown that mild exercise training at lactate threshold (LT) intensity is a safe and effective for prevention of metabolic syndrome. To elucidate the molecular mechanisms related to the beneficial effects of LT training for 60 min/day for 5 days/wk for 12 wk, we performed serial analysis of gene expression (SAGE) to examine global mRNA expression in human skeletal muscle. Approximately 57000 SAGE tags were analyzed for before training, as well as 5 days, 6 and 12 wk after the training. The LT training has coordinately induced many genes involved in mitochondrial energy metabolism, fat oxidation, glycolysis and creatine metabolism. Another molecular feature associated with this mild exercise regimen has been an induction of many genes encoding for potent antioxidant enzymes and molecular chaperons. Furthermore, the training modulated the expression levels of 233 novel transcripts. Thus, the current study reveals that LT exercise has favorably altered gene expression in human skeletal muscle to the prevention of metabolic syndrome. Keywords: transcriptome, serial analysis of gene expression, metabolic syndrome, exercise training, lactate threshold
2006-09-09 | GSE5792 | GEO
Project description:Regular physical activity is a key concept associated with a variety of health-related outcomes and successful ageing. While many of the beneficial effects of physical activity are undisputed, much of the adaptive mechanisms that lead to these benefits are not yet known. The skeletal muscle is a key contributor to physical performance and is also the target organ for many of the adaptive processes associated with exercise. Skeletal muscle is highly plastic, and changes in physical activity lead to a plethora of adaptive processes that, when repeated over time, result in structural and functional adaptations. Here we use single cell sequencing in humans to outline the effects of physical activity on cellular composition and cell type-specific processes in skeletal muscle. We show that myogenic cells in human skeletal muscle can be divided into three groups characterized by different degrees of cell maturation, and that exercise stimulates subpopulation of undifferentiated stem/progenitor myogenic cells to mature toward slow- or fast-twitch fibers. The cell type-specific adaptive mechanisms induced by exercise presented here contribute to the understanding of the skeletal muscle adaptations triggered by physical activity and may ultimately have implications for physiological and pathological processes affecting skeletal muscle, such as sarcopenia, cachexia, and glucose homeostasis.
2022-10-03 | GSE214544 | GEO
Project description:We generated a genome wide map of instances where the long noncoding RNA, Tug1, binds to DNA in cultured mouse podocytes under normal glucose conditions using Chromatin-RNA Precipitation coupled with high throughput sequencing (ChIRP-Seq) 48 alternating (even, odd) biotynilated probes were designed to span the full length of Tug1 RNA. Chromatin was prepared from gluteraldehyde crosslinked nuclei from early passage podocytes. Chromatin extracts were duplicated with either even or odd probes. Duplicate samples for Input DNA, Even pulldown (PD) and Odd PD DNA was purified following incubation and supplied for Illumina sequencing by ArrayStar (Rockville, MD).
2016-10-24 | E-GEOD-77493 | biostudies-arrayexpress