Impact of Acute Exercise on Alternative Splicing in Skeletal Muscle
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ABSTRACT:
PROVIDER: PRJNA1172289 | ENA |
REPOSITORIES: ENA
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Project description:Alternative RNA splicing (AS) is a highly conserved post-transcriptional mechanism, generating mRNA variants to diversify the proteome. Acute endurance exercise appears to transiently perturb AS in skeletal muscle, but transcriptome-wide responses are not well-defined. We aimed to better understand differential AS (DAS) in skeletal muscle by comparing short-read RNA sequencing (SRS) and long-read RNA sequencing (LRS) data. Publicly accessible SRS of clinical exercise studies were extracted from the Gene Expression Omnibus. Oxford Nanopore LRS was performed on mouse gastrocnemius before and following treadmill exercise. Differential gene expression (DGE), DAS, and isoform switching were analyzed. Western blots were performed to validate expression changes of candidate genes. Both SRS and LRS illustrated significant DGE in skeletal muscle post-exercise, whereby 57 and 15 RNA-binding proteins (RBPs) were up-/down-regulated, respectively. rMATS analysis of SRS data revealed that exon-skipping and intron-retaining splicing events were the most common. Swan analysis of LRS data revealed 38 RBPs with significant isoform switching: one of these RBPs, Hnrnpa3, underwent a significant intron-retained to protein-coding switch. HnRNP-A3 protein levels validated nearly two-fold increases at 1 hour (p=.0043) and 24 hours (p=.0103) post-exercise. This study illustrates that acute endurance exercise can elicit changes in AS-related responses and RBP expression in skeletal muscle. SRS is certainly a powerful tool for analyzing DGE but lacks AS detection. As such, “hidden” genes with no transcriptional changes but significant DAS and protein expression changes pose a major gap in knowledge. Our work highlights how LRS can uncover previously unknown transcript diversity and mechanisms influencing AS.
2025-07-30 | GSE279359 | GEO
Project description:Alternative splicing diversifies the cellular protein landscape but aberrant splicing is implicated in many diseases. We aimed to investigate to which extent mis-splicing contributes to insulin resistance as the causal defect of Type 2 Diabetes and whether diet- and exercise-based lifestyle interventions can reverse mis-splicing.
2025-03-03 | GSE253218 | GEO
Project description:Misregulated alternative splicing appears to be a major factor in the pathogenesis of myotonic dystrophy. The present study was done to further explore alternative splicing in this condition by doing exon-level analysis of mRNA from skeletal muscle of 8 subjects with type 1 myotonic dystrophy, 7 subjects with type 2 myotonic dystrophy, 8 disease controls (subjects with facioscapulohumeral muscular dystrophy), and 8 healthy controls . The ratios of signals from the various exons of a gene provided an index of altered exon inclusion/exclusion that was independent of the overall expression of that gene. There were numerous transcripts for which there was evidence of abnormal alternative splicing in subjects with myotonic dystrophy. For many of these transcripts, the abnormal splicing was confirmed by an independent RT-PCR approach. 31 subjects, one sample per subject, four groups: healthy subjects (n = 8), facioscapulohumeral dystrophy (n = 8), type 1 myotonic dystrophy (n = 8), type 2 myotonic dystrophy (n = 7)
2013-06-15 | E-GEOD-47968 | biostudies-arrayexpress
Project description:Highly expressed in skeletal muscles, the gene Obscurin (i.e. OBSCN) has 121 non-overlapping exons and codes for some of the largest known mRNAs in human genome. Furthermore, it is known to play an essential role in muscle development and function. Mutations within OBSCN are known to cause several hypertrophic cardiomyopathies and muscular disorders. Even though OBSCN undergoes extensive alternative splicing, its splicing regulation associated with skeletal and cardiac muscle development has not previously been thoroughly studied. We study splicing of OBSCN in skeletal and cardiac muscles extracted from 41 postnatal individuals and 6 fetuses. We detect several splicing regulations located in 5’end, 3’ end, as well as in the middle of OBSCN. Many of these alternative splicing events have not previously been reported. These findings are essential for an accurate pre- and postnatal diagnosis and prognosis of OBSCN exonic variants. The muscle development OBSCN exon inclusion map is available at https://gacatag.shinyapps.io/OBSCN_PSIVIS/ .
2025-02-24 | GSE270408 | GEO
Project description:Misregulated alternative splicing appears to be a major factor in the pathogenesis of myotonic dystrophy. The present study was done to further explore alternative splicing in this condition by doing exon-level analysis of mRNA from skeletal muscle of 8 subjects with type 1 myotonic dystrophy, 7 subjects with type 2 myotonic dystrophy, 8 disease controls (subjects with facioscapulohumeral muscular dystrophy), and 8 healthy controls . The ratios of signals from the various exons of a gene provided an index of altered exon inclusion/exclusion that was independent of the overall expression of that gene. There were numerous transcripts for which there was evidence of abnormal alternative splicing in subjects with myotonic dystrophy. For many of these transcripts, the abnormal splicing was confirmed by an independent RT-PCR approach.
2013-06-15 | GSE47968 | GEO
Project description:A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA binding protein Rbm24 is a major regulator of muscle specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protein. We built linear models using 2 different experiments and two conditions (miR222 over expression (n=1) and control siRNA(n=2)) with the linear formula (~condition + experiment).
2016-08-22 | E-GEOD-75981 | biostudies-arrayexpress
Project description:Exercise promoted skeletal muscle growth in adolescents through facilitating MyoD mRNA stability of MuSCs in a Mettl3-mediated m6A dependent manner. The methyl donor betaine could be a potential alternative to exercise for promoting adolescent skeletal muscle growth by directly augmenting the global levels of m6A methylation. These findings may provide a theoretical foundation for encouraging daily fitness exercise and ensuring healthy growth in adolescents.
2024-12-18 | GSE278365 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE18583: Baseline skeletal muscle gene expression GSE35659: A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype (resting muscle after endurance training) Refer to individual Series
2012-02-10 | E-GEOD-35661 | biostudies-arrayexpress
Project description:Lifestyle-induced changes in alternative splicing patterns in mice [skeletal muscle]
| PRJNA1064582 | ENA
Project description:The few investigations on exercise-induced global gene expression responses in human skeletal muscle haves typically focused at one specific mode of exercise and few such studies have implemented control measures. However, interpretation on distinct phenotype regulation necessitate comparison between essentially different modes of exercise and the ability to identify true exercise effects, necessitate implementation of independent non-exercise control subjects. Furthermore, muscle transkriptometranscriptome data made available through previous exercise studies can be difficult to extract and interpret by individuals that are inexperienced with bioinformatic procedures. In a comparative study, we; (1) investigated the human skeletal muscle transcriptome response to differentiated exercise and non-exercise control intervention, and; (2) aimed to develop a straightforward search tool to allow for easy extraction and interpretation of our data. We provide a simple spreadsheet containing transcriptome data allowing other investigators to see how mRNA of their interest behave in skeletal muscle following exercise, both endurance, strength and non-exercise. Our approach, allow investigators easy access to information on genuine transcriptome effects of differentiated exercise, to better aid hyporthesis-driven question in this particular field of research. 18 subjects were divided into 3 groups, performing 12 weeks of Endurance or Strength training or no training. Biopsies for microarray were take before (Pre) and 2½ and 5 hours after the last training session. Isolated RNA from these biopsies were then measured with the Affymetrix Human Gene 1.0 ST arrays.
2014-11-19 | E-GEOD-59088 | biostudies-arrayexpress