ORCID Profile
0000-0002-4654-0868
Current Organisation
Deakin University
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Publisher: Cold Spring Harbor Laboratory
Date: 28-04-2022
DOI: 10.1101/2022.04.27.489477
Abstract: Mitochondria are central to cellular function, particularly in metabolically active tissues such as skeletal muscle. Non-coding RNAs (ncRNAs) typically localise within the nucleus and cytosol but may also translocate to subcellular compartments such as mitochondria. We aimed to investigate the nuclear-encoded ncRNAs that localise within the mitochondria of skeletal muscle cells and tissue. Intact mitochondria were isolated via immunoprecipitation and an enzymatic digestion approach was optimised to remove transcripts located exterior to mitochondria, making it amenable for high-throughput transcriptomic sequencing. Small-RNA sequencing libraries were successfully constructed from as little as 1.8ng mitochondrial RNA input. Small-RNA and whole transcriptome sequencing of mitochondria reveals the enrichment of over 200 miRNAs and 200 lncRNAs that have not previously been observed within skeletal muscle mitochondria. In summary, we describe a novel, powerful sequencing approach applicable to animal and human tissues and cells that reveals the unexpected ersity of nuclear-encoded ncRNA transcripts localised within skeletal muscle mitochondria.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2022
DOI: 10.1186/S12915-022-01366-4
Abstract: Mitochondria 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. In 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 Ca 2+ -mediated stimulus, Tug1 KD prevented an increase in Ppargc1a expression. RNA sequencing revealed that Tug1 KD impacted mitochondrial Ca 2+ 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. We 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.
Publisher: Wiley
Date: 31-07-2018
DOI: 10.1113/EP086846
Publisher: Wiley
Date: 08-2020
DOI: 10.14814/PHY2.14520
No related grants have been discovered for Jessica Silver.