bims-musmir Biomed News
on microRNAs in muscle
Issue of 2025–08–17
twelve papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway
  1. Promoting mitochondrial fusion is protective against cancer-induced muscle detriments in males and females.
  2. Tribbles 3 blunts exercise-induced skeletal muscle adaptation.
  3. Analyzing RNA Localization Using the RNA Proximity Labeling Method OINC-seq.
  4. Distinct Endothelial Gene Responses to Acute Exercise in Skeletal Muscle.
  5. An Iron-regulated Signalling Pathway Controls Adipose Browning and Cancer Cachexia.
  6. Identification of CaVβ1 Isoforms Required for Neuromuscular Junction Formation and Maintenance.
  7. Sepsis Induces Long-Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A.
  8. Mitochondrial function is impaired in long COVID patients.
  9. Long non-coding RNA EPB41L4A-AS1 as a biomarker of sepsis alleviates inflammatory response by targeting miR-146a-5p.
  10. Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy.
  11. RNA triggers chronic stress during neuronal aging.
  12. Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a post-transcriptional influence.
  1. BMC Cancer. 2025 Aug 11. 25(1): 1300
    Promoting mitochondrial fusion is protective against cancer-induced muscle detriments in males and females.
    Francielly Morena, Seongkyun Lim, Ana Regina Cabrera, Toby L Chambers, Pieter J Koopmans, Stavroula Tsitkanou, Sabin Khadgi, Calvin Peterson, Eleanor R Schrems, Ruqaiza Muhyudin, Sepideh Shakeri, Kevin Zhao, Devan Mishra, Tyrone A Washington, Kevin A Murach, Nicholas P Greene.
       BACKGROUND: Skeletal muscle atrophy during cancer-induced cachexia remains a significant challenge in cancer management. Mitochondrial defects precede muscle mass and functional losses in models of cancer cachexia (CC). We hypothesized targeting Opa1-a key regulator of mitochondrial fusion-can attenuate LLC-induced CC outcomes.
    METHODS: We utilized 1) in vivo transgenic Opa1 overexpression (OPA1 TG) in LLC-induced CC in vivo, and 2) BPG15 administration to induce Opa1 in vitro and in vivo.
    RESULTS: OPA1 TG attenuated plantaris, gastrocnemius, and EDL loss with LLC in males and alleviated gastrocnemius loss in females. OPA1 TG had greater mitochondrial respiration in plantaris and white gastrocnemius, and lowered pMitoTimer Red Puncta (-63%), a proxy for mitophagy in males. OPA1 TG protected muscle contractility at physiological stimulation frequencies by up to 60% in female LLC mice. OPA1 TG enhanced the ratio of OPA1/DRP1 protein content-a proxy for fusion and fission balance-in males and females. In vitro, BGP-15 attenuated LLC conditioned media-induced myotube atrophy by ~ 9% concomitant with suppression of the transcriptional factor FoxO3, autophagy markers, and inflammatory cytokines. In vivo, BGP-15 improved contractility at lower frequencies (10-60 Hz), with LLC-BGP-15 showing up to 20% greater torque than LLC-control. BGP-15 treated LLC animals had 71% fewer pMitoTimer red puncta, suggesting attenuated mitophagy.
    CONCLUSIONS: Promoting mitochondrial fusion via OPA1 induction improved cachectic outcomes in mice. Targeting OPA1providing provides a promising therapeutic approach for CC treatment.
    Keywords:  BGP-15; Lewis Lung Carcinoma; Mitochondrial dynamics; Muscle contractility; OPA1
    DOI:  https://doi.org/10.1186/s12885-025-14630-x
  2. bioRxiv. 2025 Jul 19. pii: 2025.07.16.665065. [Epub ahead of print]
    Tribbles 3 blunts exercise-induced skeletal muscle adaptation.
    Ran Hee Choi, Abigail McConahay, Mackenzie B Johnson, Morgan Ojemuyiwa, Brooklyn J Phillips, Ha-Won Jeong, Ho-Jin Koh.
      Tribbles 3 (TRB3) is a pseudokinase and its expression has been shown to disrupt glucose metabolism through the inhibition of Akt under obese and diabetic conditions. We recently found that overexpression of TRB3 in mouse skeletal muscle decreased skeletal muscle mass and function, leading to muscle atrophy. Here, we examined whether TRB3 affects exercise training-induced skeletal muscle adaptation. We trained muscle-specific TRB3 transgenic (TG) and wild-type (WT) littermates using a voluntary wheel running protocol for 6 weeks and found that TG mice ran significantly less weekly distances than WT littermates. To exclude the possibility that different skeletal muscle adaptations would be produced due to different training intensities, involuntary treadmill exercise (TM) was used as a training regimen. At the 5 th week of training, we measured glucose tolerance and found that trained TG mice showed glucose intolerance compared to WT littermates. Furthermore, overexpression of TRB3 significantly suppressed the expression of genes needed for glucose uptake and mitochondrial biogenesis, independent of training status. To further determine the role of TRB3 in exercise-induced adaptation, TRB3 knockout (KO) mice were trained by voluntary and involuntary exercise protocols. KO mice presented improved glucose tolerance compared to WT littermates independent of training status. However, we did not observe significant change in the expression of markers for glucose uptake and mitochondrial biogenesis. Taken together, our results indicate that TRB3 in skeletal muscle blunts the benefits of exercise-induced skeletal muscle adaptation.
    DOI:  https://doi.org/10.1101/2025.07.16.665065
  3. Bio Protoc. 2025 Aug 05. 15(15): e5403
    Analyzing RNA Localization Using the RNA Proximity Labeling Method OINC-seq.
    Megan C Pockalny, Hei-Yong G Lo, Raeann Goering, J Matthew Taliaferro.
      Thousands of RNAs are localized to specific subcellular locations, and these localization patterns are often required for optimal cell function. However, the sequences within RNAs that direct their transport are unknown for almost all localized transcripts. Similarly, the RNA content of most subcellular locations remains unknown. To facilitate the study of subcellular transcriptomes, we developed the RNA proximity labeling method OINC-seq. OINC-seq utilizes photoactivatable, spatially restricted RNA oxidation to specifically label RNA in proximity to a subcellularly localized bait protein. After labeling, these oxidative RNA marks are then read out via high-throughput sequencing due to their ability to induce predictable misincorporation events by reverse transcriptase. These induced mutations are then quantitatively assessed for each gene using our software package PIGPEN. The observed mutation rate for a given RNA species is therefore related to its proximity to the localized bait protein. This protocol describes procedures for assaying RNA localization via OINC-seq experiments as well as computational procedures for analyzing the resulting data using PIGPEN. Key features • OINC-seq assays the RNA content of a variety of subcellular locations. • OINC-seq utilizes a photoactivatable, proximity-dependent RNA oxidation reaction to label RNAs. • Oxidative RNA marks are read using high-throughput sequencing without the need for enrichment. • Oxidative RNA marks are identified and quantified using the associated PIGPEN software.
    Keywords:  Proximity labeling; RNA localization; RNA modifications; RNA oxidation; RNA trafficking
    DOI:  https://doi.org/10.21769/BioProtoc.5403
  4. Am J Physiol Endocrinol Metab. 2025 Aug 11.
    Distinct Endothelial Gene Responses to Acute Exercise in Skeletal Muscle.
    Adele Addington, Rebecca M Wall, Xiaoran Wei, Sarah D Frate, Michelle L Olsen, Joshua C Drake, Siobhan Craige.
      Acute exercise causes a short-term stress, activating immediate gene expression responses. These responses are essential for cellular adaptation and resilience. Endothelial cells, positioned throughout the vasculature, play a central role in sensing and responding to these stress signals. As dynamic regulators of vascular tone, nutrient delivery, and cellular communication, endothelial cells are key integrators of metabolic adaptation. They coordinate intra- and inter-organ communication through the release of signaling molecules, shaping systemic responses to exercise. Despite their importance, the endothelial cell-specific transcriptional response to exercise remains poorly understood. To interrogate the transcriptional response to exercise in endothelial cells, we used NuTRAP (Nuclear Tagging and Translating Ribosome Affinity Purification) mouse technology which express EGFP/L10a under control of the vascular endothelial-cadherin promoter (NuTRAPEC). Following a single bout of acute exercise, ribosome-associated mRNA was isolated from endothelial cells from gastrocnemius of both exercised and sedentary animals. RNA sequencing confirmed endothelial cell-specific enrichment and revealed robust changes in gene expression. Exercise induced canonical early response genes (Nr4a2, Sik1, Slc25a25) and activated pathways related to angiogenesis, oxidative stress, stress kinase signaling, vascular remodeling and metabolic stress signaling. For context, we analyzed skeletal muscle fiber responses using NuTRAP mice driven by the human alpha-skeletal actin (NuTRAPSMF) mice. While some genes overlapped, skeletal muscle fiber-enriched pathways included hypoxia response and muscle development. These findings reveal a distinct microvascular endothelial transcriptional signature in skeletal muscle tissue in response to acute exercise, providing insight into the cell-type-specific mechanisms that underlie vascular adaptation and intercellular communication in response to physiologic stressors like exercise.
    Keywords:  Acute exercise; endothelial cells; exerkines; transcriptomics; upstream regulators
    DOI:  https://doi.org/10.1152/ajpendo.00250.2025
  5. bioRxiv. 2025 Jul 18. pii: 2025.07.16.664180. [Epub ahead of print]
    An Iron-regulated Signalling Pathway Controls Adipose Browning and Cancer Cachexia.
    Jung Seung Nam, Maya S Dixon, Pardis Ahmadi, Kathrin Schilling, Samuel Pan, Yuxuan Chen, Nal Ae Yoon, Yanping Sun, Jordan Lu, Shu Ichimiya, Jeanine M Genkinger, Thomas C Caffrey, Kelsey A Klute, Benjamin J Swanson, Paul Grandgenett, Michael A Hollingsworth, Kazuki Sugahara, Michael D Kluger, Anthony Ferrante, Sabrina Diano, Iok In Christine Chio.
      The browning and atrophy of white adipose tissue (WAT) are early events in cachexia, a lethal metabolic disorder affecting nearly half of cancer patients, including those with pancreatic ductal adenocarcinoma (PDA). Using patient-derived specimens and PDA mouse models, we identified perturbations in iron metabolism and proteinaceous methionine oxidation as key initiating events of adipose browning. In particular, the iron influxes that accompany WAT browning induce the activity of methionine sulfoxide reductase A (MSRA), an enzyme that reverses the oxidation of proteinaceous methionine residues. Mechanistically, iron coordination by the conserved iron-binding motifs (E203-xx-H206) of two MSRA polypeptides serves to multimerize, stabilize, and enzymatically activate MSRA. This in turns facilitates adipose browning by maintaining the reduced state of two methionines near the ATP-binding site of Protein Kinase A (PKA). Remarkably, in mouse models of PDA, MsrA deletion impairs WAT browning, significantly mitigates cachexia, and improves the overall survival of tumor-bearing animals. By establishing the iron-MSRA-PKA axis as a key nexus of cancer-associated cachexia, our study offers new perspectives for the treatment of this condition.
    DOI:  https://doi.org/10.1101/2025.07.16.664180
  6. Cells. 2025 Aug 06. pii: 1210. [Epub ahead of print]14(15):
    Identification of CaVβ1 Isoforms Required for Neuromuscular Junction Formation and Maintenance.
    Amélie Vergnol, Aly Bourguiba, Stephanie Bauché, Massiré Traoré, Maxime Gelin, Christel Gentil, Sonia Pezet, Lucile Saillard, Pierre Meunier, Mégane Lemaitre, Julianne Perronnet, Frederic Tores, Candice Gautier, Zoheir Guesmia, Eric Allemand, Eric Batsché, France Pietri-Rouxel, Sestina Falcone.
      Voltage-gated Ca2+ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1-CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in skeletal muscle as multiple isoforms. The adult isoform, CaVβ1D, localizes at the triad and modulates CaV1 activity during Excitation-Contraction Coupling (ECC). In this study, we investigated the lesser-known embryonic/perinatal CaVβ1 isoforms and their roles in neuromuscular junction (NMJ) formation, maturation, and maintenance. We found that CaVβ1 isoform expression is developmentally regulated through differential promoter activation. Specifically, CaVβ1A is expressed in embryonic muscle and reactivated in denervated adult muscle, alongside the known CaVβ1E isoform. Nerve injury in adult muscle triggers a shift in promoter usage, resulting in re-expression of embryonic/perinatal Cacnb1A and Cacnb1E transcripts. Functional analyses using aneural agrin-induced AChR clustering on primary myotubes demonstrated that these isoforms contribute to NMJ formation. Additionally, their expression during early post-natal development is essential for NMJ maturation and long-term maintenance. These findings reveal previously unrecognized roles of CaVβ1 isoforms beyond VGCC regulation, highlighting their significance in neuromuscular system development and homeostasis.
    Keywords:  CaVβ isoforms; Cacnb1; Long-read sequencing; neuromuscular junctions; promoters; skeletal muscle
    DOI:  https://doi.org/10.3390/cells14151210
  7. J Cachexia Sarcopenia Muscle. 2025 Aug;16(4): e70041
    Sepsis Induces Long-Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A.
    Alexandre Pierre, Raphael Favory, Benoit Brassart, Claire Bourel, Raphael Romien, Sylvain Normandin, Arthur Dubech, Claire Vincent, Jeremy Lemaire, Gaelle Grolaux, Ophelie Not, Frederic Wallet, Frederic Daussin, Eric Boulanger, Arthur Durand, Marie Frimat, Alina Ghinet, Michael Howsam, William Laine, Philippe Marchetti, Jerome Kluza, Estelle Chatelain, Jimmy Vandel, Nicolas Barois, Valerie Montel, Bruno Bastide, Sebastien Preau, Steve Lancel.
       BACKGROUND: Sepsis survivors often experience sustained muscle weakness, leading to physical disability, with no pharmacological treatments available. Despite these well-documented long-term clinical consequences, research exploring the cellular and molecular mechanisms is sorely lacking.
    METHODS: Bioinformatic analysis was performed in the vastus lateralis transcriptome of human ICU survivors 7 days after ICU discharge (D7), 6 months (M6) and age- and sex-matched controls. Enrichment analysis using Gene Ontology (GO) terms and Mitocarta3.0 was performed at D7 and M6 on differentially expressed genes (DEGs) and modules identified by weighted gene co-expression network analysis (WGCNA). Using a murine model of resuscitated sepsis induced by caecal slurry injection, pathways identified by the bioinformatics analysis were explored in 18- to 24-week-old sepsis-surviving (SS) mice at Day 10. Autophagy flux was investigated both in vivo and in vitro with chloroquine, a lysosomal inhibitor and urolithin A (UA), an autophagy inducer. Systemic metabolism was evaluated with indirect calorimetry, muscle phenotype with in situ and ex vivo contractility, muscle mass, myofibre cross-sectional area and typing and mitochondrial population with transmission electron microscopy (TEM), as well as mitochondrial function with high-resolution respirometry. Autophagic vacuole (AV) level was monitored using LC3B-II and P62 protein expression and TEM.
    RESULTS: Pathways related to 'mitochondrion' were the only ones whose deregulation persisted between D7 and M6 (p < 0.05) and characterized WGCNA modules correlated with muscle mass, strength and physical function. Shared mitochondrial DEGs between D7 and M6 encoded matrix mitochondrial proteins related to 'metabolism' and 'mitochondrial dynamics'. SS mice exhibited reduced complex I-driven oxygen consumption (CI-JO2) (-45%), increased S-nitrosylation of complex I, damaged (+35%) and oxidized (+51%) mitochondria and AV accumulation (5 vs. 50 AVs/mm2) compared with sham pair-fed mice (p < 0.05) despite no differences in mitochondrial size or number. Autophagy flux was reduced in SS mice due to decreased AV degradation ratio (p < 0.05). UA restored a balanced autophagy flux (turnover ratio 0.96 vs. -0.17) by increasing AVs formation and degradation ratio (p < 0.05). UA also improved CI-JO2 (81 vs. 106 pmol/s/mg), tetanic force (215 vs. 244 mN/mm2) and hindlimb muscle weight in SS mice (p < 0.05).
    CONCLUSION: Mitochondrial and autophagy disruption contributes to long-term muscle dysfunction in human and mouse sepsis survivors. We demonstrate for the first time that sepsis induces an autophagy flux blockade. Urolithin A prevents mitochondrial and muscle impairments both in vivo and in vitro by improving autophagy flux.
    Keywords:  autophagy; mitochondria; muscle; sepsis
    DOI:  https://doi.org/10.1002/jcsm.70041
  8. Ann Med. 2025 Dec;57(1): 2528167
    Mitochondrial function is impaired in long COVID patients.
    Jane Macnaughtan, Kai-Yin Chau, Ewen Brennan, Marco Toffoli, Antonella Spinazzola, Toby Hillman, Melissa Heightman, Anthony Henry Vernon Schapira.
       BACKGROUND: The Long COVID syndrome is a major global health problem, affecting approximately 10-20% of individuals infected with SARS-CoV-2 virus with many remaining symptomatic beyond one year. Fatigue, reduced exercise tolerance and hyperlactataemia on minimal exertion have led to the suggestion of a bioenergetic defect. We hypothesised that mitochondrial dysfunction is a pathological feature in Long COVID cases and would correlate with clinical outcome.
    METHODS: This prospective, case-controlled, observational study recruited 27 participants with an established diagnosis of Long COVID syndrome from a single tertiary clinic together with 16 age-matched controls aged 25-65 years. Seahorse-based mitochondrial flux analysis and bioenergetics profile of isolated peripheral blood mononuclear cells (PBMCs) was performed and correlated with clinical phenotype.
    FINDINGS: Long COVID cases had an increased baseline and ATP-induced oxygen consumption rate with a significant attenuation in tetramethylrhodamine methyl ester perchlorate fluorescence response to oligomycin. Correlations were observed between mitochondrial function and autonomic health, quality of life and time from index infection. Sex-specific differences were also observed.
    INTERPRETATION: PBMCs from Long COVID subjects exhibit an exceptional and distinctive change in ATP synthase, as it contributes to the mitochondrial membrane potential rather than using it exclusively to generate ATP. The findings suggest that the enzyme runs both forward and reverse reactions, synthesising and hydrolysing ATP. The correlation of mitochondrial function with clinical phenotype in Long COVID may indicate a causal relationship and warrants further validation in larger scale studies.
    Keywords:  ATP synthase; long COVID; mitochondrial dysfunction; peripheral blood mononuclear cells (PBMCs)
    DOI:  https://doi.org/10.1080/07853890.2025.2528167
  9. Eur J Med Res. 2025 Aug 11. 30(1): 728
    Long non-coding RNA EPB41L4A-AS1 as a biomarker of sepsis alleviates inflammatory response by targeting miR-146a-5p.
    Weigui Zhou, Chan Li, Huixian Yun, Ningning Zhang, Rui Zhang.
       OBJECTIVE: The prognosis of sepsis, a pathological condition associated with high mortality and rapid progression, can be improved with precise diagnosis, effective treatment, and nursing care. This study investigated the expression and clinical significance of the long non-coding RNA (lncRNA) EPB41L4A-AS1 in sepsis.
    METHODS: The serum EPB41L4A-AS1 levels in patients with sepsis were quantified using quantitative real-time polymerase chain reaction (RT-qPCR). The diagnostic value of EPB41L4A-AS1 was determined using the receiver operating characteristic curves. The correlation of EPB41L4A-AS1 with clinical parameters was evaluated using Pearson correlation. Kaplan-Meier assessment of prognostic value. Lipopolysaccharide (LPS)-treated THP-1 cells served as an in vitro cell model for sepsis. The mRNA and protein levels of inflammatory factors were examined using RT-qPCR analysis and enzyme-linked immunosorbent assay, respectively. Finally, the binding of EPB41L4A-AS1 to miR-146a-5p was determined using the dual-luciferase reporter and RNA immunoprecipitation assays.
    RESULTS: EPB41L4A-AS1 was significantly downregulated in patients with sepsis. The downregulation was inversely correlated with inflammatory cytokines and severity scores (APACHE II and SOFA). EPB41L4A-AS1 expression had a high diagnostic value in sepsis. The overexpression of EPB41L4A-AS1 downregulated inflammatory factor expression and release. However, miR-146a-5p mitigated the inhibitory effects of EPB41L4A-AS1 overexpression on inflammatory factors expression and release. EPB41L4A-AS1 was a target of miR-146a-5p.
    CONCLUSION: lncRNA EPB41L4A-AS1 alleviates sepsis-related inflammation by targeting miR-146a-5p and may serve as a diagnostic biomarker for sepsis.
    Keywords:  EPB41L4A-AS1; Molecular mechanism; Sepsis; miR-146a-5p
    DOI:  https://doi.org/10.1186/s40001-025-02991-9
  10. Nat Commun. 2025 Aug 09. 16(1): 7367
    Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy.
    Bishal Basak, Erika L F Holzbaur.
      Mutations that disrupt the clearance of damaged mitochondria via mitophagy are causative for neurological disorders including Parkinson's. Here, we identify a Mitophagic Stress Response (MitoSR) activated by mitochondrial damage in neurons and operating in parallel to canonical Pink1/Parkin-dependent mitophagy. Increasing levels of mitochondrial stress trigger a graded response that induces the concerted degradation of negative regulators of autophagy including Myotubularin-related phosphatase (MTMR)5, MTMR2 and Rubicon via the ubiquitin-proteasome pathway and selective proteolysis. MTMR5/MTMR2 inhibit autophagosome biogenesis; consistent with this, mitochondrial engulfment by autophagosomes is enhanced upon MTMR2 depletion. Rubicon inhibits lysosomal function, blocking later steps of neuronal autophagy; Rubicon depletion relieves this inhibition. Targeted depletion of both MTMR2 and Rubicon is sufficient to enhance mitophagy, promoting autophagosome biogenesis and facilitating mitophagosome-lysosome fusion. Together, these findings suggest that therapeutic activation of MitoSR to induce the selective degradation of negative regulators of autophagy may enhance mitochondrial quality control in stressed neurons.
    DOI:  https://doi.org/10.1038/s41467-025-62379-5
  11. bioRxiv. 2025 Aug 05. pii: 2025.08.04.668575. [Epub ahead of print]
    RNA triggers chronic stress during neuronal aging.
    Kevin Rhine, Elle Epstein, Natasha M Carlson, Xuezhen Ge, Orel Mizrahi, Anika Kamat, Anita Hermann, William R Brothers, John Ravits, Eric J Bennett, Gülçin Pekkurnaz, Gene W Yeo.
      Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. Cellular stress can arise from several sources, but there is significant disagreement about which stress might contribute to aging and neurodegeneration. Here, we leverage directed transdifferentiation of human fibroblasts into aged neurons to determine the source of ISR activation. We demonstrate that increased accumulation of cytoplasmic double-stranded RNA (dsRNA) activates the eIF2α kinase PKR, which in turn triggers the ISR in aged neurons and leads to sequestration of dsRNA in stress granules. Aged neurons accumulate endogenous mitochondria-derived dsRNA that directly binds to PKR. This mitochondrial dsRNA leaks through damaged mitochondrial membranes and forms cytoplasmic foci in aged neurons. Finally, we demonstrate that PKR inhibition leads to the cessation of stress, resumption of cellular translation, and restoration of RNA-binding protein expression. Together, our results identify a source of RNA stress that destabilizes aged neurons and may contribute to neurodegeneration.
    DOI:  https://doi.org/10.1101/2025.08.04.668575
  12. Am J Physiol Cell Physiol. 2025 Aug 11.
    Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a post-transcriptional influence.
    Ryan A Martin, Xiping Zhang, Mark R Viggars, James A Sanford, Zane W Taylor, Joshua R Hansen, Geremy C Clair, Collin M Douglas, Stuart James Hesketh, Joshua N Adkins, Karyn A Esser.
      Exercise is firmly established as a key contributor to overall well-being and is frequently employed as a therapeutic approach to mitigate various health conditions. One pivotal aspect of the impact of exercise lies in the systemic transcriptional response, which underpins its beneficial adaptations. While extensive research has been devoted to understanding the transcriptional response to exercise, our knowledge of the protein constituents of nuclear processes accompanying gene expression in skeletal muscle remains largely elusive. We hypothesize that alterations in the nuclear proteome following exercise hold vital clues for comprehending exercise-induced transcriptional regulation and related nuclear functions. We first detail the successful isolation of skeletal muscle nuclei from C57BL/6 mice encapsulating 2,030 proteins linked to nuclear processes such as transcription, RNA processing, chromatin modifications, and nuclear transport. We then used this approach to isolate muscle nuclei in sedentary, immediately post-, 1-hour, and 4-hours after a 30-minute treadmill running session, to gain insight into the nuclear proteome after exercise. We found 54 proteins linked to mRNA splicing and nucleocytoplasmic transport, many of which were substantially reduced immediately post-exercise followed by a rapid increase 1- and 4-hours post-exercise. Super resolution microscopy experiments highlight localization changes in mRNA processing proteins post-exercise, further suggesting changes in nuclear transport dynamics. Our data provides important insight into changes in the nuclear proteome following exercise. In particular it highlights proteins contributing to mRNA processing and splicing in addition to transcriptional processes with exercise offering broader changes in mechanisms modulating the molecular response to acute exercise.
    Keywords:  Exercise; Muscle; Nuclear Proteome; Nuclei; Proteome
    DOI:  https://doi.org/10.1152/ajpcell.00575.2024
This page is being maintained by Thomas Krichel. It was last updated on 2025‒09‒08 at 9:20.