PMID- 35850762 OWN - NLM STAT- MEDLINE DCOM- 20220721 LR - 20220725 IS - 1741-7007 (Electronic) IS - 1741-7007 (Linking) VI - 20 IP - 1 DP - 2022 Jul 18 TI - Long non-coding RNA Tug1 modulates mitochondrial and myogenic responses to exercise in skeletal muscle. PG - 164 LID - 10.1186/s12915-022-01366-4 [doi] LID - 164 AB - BACKGROUND: 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-1alpha), 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-1alpha in regulating transcriptional responses to exercise in skeletal muscle. RESULTS: In human skeletal muscle, TUG1 gene expression was upregulated post-exercise and was also positively correlated with the increase in PGC-1alpha 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-1alpha 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. CONCLUSIONS: 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. CI - (c) 2022. The Author(s). FAU - Trewin, Adam J AU - Trewin AJ AUID- ORCID: 0000-0001-7322-4054 AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. a.trewin@deakin.edu.au. FAU - Silver, Jessica AU - Silver J AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. FAU - Dillon, Hayley T AU - Dillon HT AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. AD - Human Integrated Physiology and Sports Cardiology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia. FAU - Della Gatta, Paul A AU - Della Gatta PA AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. FAU - Parker, Lewan AU - Parker L AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. FAU - Hiam, Danielle S AU - Hiam DS AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. AD - Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia. FAU - Lee, Yin Peng AU - Lee YP AD - Genomics Centre, School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, Victoria, Australia. FAU - Richardson, Mark AU - Richardson M AD - Genomics Centre, School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, Victoria, Australia. FAU - Wadley, Glenn D AU - Wadley GD AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. FAU - Lamon, Severine AU - Lamon S AD - Institute for Physical Activity and Nutrition, and School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia. severine.lamon@deakin.edu.au. LA - eng SI - figshare/10.6084/m9.figshare.20175770 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220718 PL - England TA - BMC Biol JT - BMC biology JID - 101190720 RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (RNA, Long Noncoding) RN - 0 (TUG1 long noncoding RNA, human) RN - 0 (long non-coding RNA TUG1, mouse) SB - IM MH - Animals MH - Energy Metabolism MH - Humans MH - Mice MH - Mitochondria/metabolism MH - Muscle Development/genetics MH - Muscle, Skeletal/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism MH - RNA, Long Noncoding/*genetics/metabolism PMC - PMC9295458 OTO - NOTNLM OT - Bioenergetics OT - Muscle OT - Non-coding RNA OT - Transcriptome COIS- The authors declare that they have no competing interests. EDAT- 2022/07/20 06:00 MHDA- 2022/07/22 06:00 PMCR- 2022/07/18 CRDT- 2022/07/19 07:46 PHST- 2021/11/07 00:00 [received] PHST- 2022/07/05 00:00 [accepted] PHST- 2022/07/19 07:46 [entrez] PHST- 2022/07/20 06:00 [pubmed] PHST- 2022/07/22 06:00 [medline] PHST- 2022/07/18 00:00 [pmc-release] AID - 10.1186/s12915-022-01366-4 [pii] AID - 1366 [pii] AID - 10.1186/s12915-022-01366-4 [doi] PST - epublish SO - BMC Biol. 2022 Jul 18;20(1):164. doi: 10.1186/s12915-022-01366-4.