scholarly journals Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions

2017 ◽  
Author(s):  
Amy E. Brinegar ◽  
Zheng Xia ◽  
James A. Loehr ◽  
Wei Li ◽  
George G. Rodney ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Alternative Splicing ◽  
Postnatal Development ◽  
Muscle Development ◽  
Muscle Relaxation ◽  
Calcium Handling ◽  
Muscle Physiology ◽  
Mouse Muscle ◽  
Calcium Dependent ◽  
Calcineurin A

AbstractPostnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first two weeks after birth are particularly dynamic for differential gene expression and AS transitions, and calciumhandling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin targets Nfatc3 and Nfatc2, and affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of AS during muscle postnatal development.

scholarly journals Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Amy E Brinegar ◽  
Zheng Xia ◽  
James Anthony Loehr ◽  
Wei Li ◽  
George Gerald Rodney ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Alternative Splicing ◽  
Postnatal Development ◽  
Muscle Development ◽  
Muscle Relaxation ◽  
Calcium Handling ◽  
Muscle Physiology ◽  
Mouse Muscle ◽  
Calcium Dependent ◽  
Calcineurin A

Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here, we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development.

Cloning and characterization of a myoblast cell surface antigen defined by 24.1D5 monoclonal antibody

Development ◽  
1989 ◽  
Vol 105 (4) ◽  
pp. 723-731 ◽  
Author(s):  
H.J. Gower ◽  
S.E. Moore ◽  
G. Dickson ◽  
V.L. Elsom ◽  
R. Nayak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Monoclonal Antibody ◽  
Cell Surface ◽  
Human Skeletal Muscle ◽  
Muscle Development ◽  
Early Stage ◽  
Primary Cultures ◽  
Skeletal Muscle Development ◽  
Mouse Muscle ◽  
Human Skeletal Muscle Cells

Monoclonal antibody 24.1D5 reacts specifically with an epitope expressed on the cell surface of mononucleate myoblasts in primary cultures of human skeletal muscle cells, but not with either multinucleate myotubes or fibroblasts. Polypeptides of 60 and 100 X 10(3) Mr were identified by immunoblotting with the McAb. Human muscle cDNAs encoding the 24.1D5 epitope were used to study further the structure and expression of 24.1D5 during skeletal muscle development. Two mRNA species of 3.0 and 2.5 kb were identified in primary cultures of human skeletal muscle and in mouse muscle cell lines. The levels of both transcripts decreased during myotube formation in vitro and were similarly decreased during myogenesis in the mouse embryo. 24.1D5 mRNAs were expressed by multipotential cells and myoblast derivatives of the mouse embryonic cell line C3H10T1/2, suggesting that 24.1D5 is expressed at an early stage during skeletal muscle development.

scholarly journals Trim33 (Tif1γ) is not required for skeletal muscle development or regeneration but suppresses cholecystokinin expression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cassie A. Parks ◽  
Katherine Pak ◽  
Iago Pinal-Fernandez ◽  
Wilson Huang ◽  
Assia Derfoul ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Knockout Mice ◽  
Muscle Regeneration ◽  
Skeletal Muscles ◽  
Muscle Development ◽  
Conditional Knockout ◽  
C2c12 Cells ◽  
Mouse Muscle ◽  
Muscle Histology

AbstractThe expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.

scholarly journals Plasminogen activator in mammalian skeletal muscle: characteristics of effect of denervation on urokinase-like and tissue activator.

1986 ◽  
Vol 103 (4) ◽  
pp. 1415-1421 ◽  
Author(s):  
B W Festoff ◽  
D Hantaï ◽  
J Soria ◽  
A Thomaïdis ◽  
C Soria
Keyword(s):  
Skeletal Muscle ◽  
Basement Membrane ◽  
Plasminogen Activator ◽  
Muscle Development ◽  
Neuromuscular Diseases ◽  
Young Male ◽  
Mammalian Skeletal Muscle ◽  
Mouse Muscle ◽  
Sciatic Neurectomy ◽  
Molecular Masses

Analyses were made of the fibrinolytic, plasminogen-activating system in skeletal muscle to determine if a regulating influence of the nerve could be detected on these enzymes. Young male mice underwent right sciatic neurectomy. Extracts were prepared from denervated muscle at 2-17 d after axotomy and compared with controls. Using a cascade-style biochemical assay (Rånby, M., B. Norrman, and P. Wallén, 1982, Thromb. Res., 27:743-748) we found that low levels of plasminogen activator (PA) were present in adult, innervated mouse muscle, but that denervation resulted in a marked time-dependent increase in enzyme activity. Qualitative separation showed an eightfold increase in urokinase-like PA with moderate elevation of tissue PA activity after 10 d. Fibrin zymography (Granelli-Piperno, A., and E. Reich, 1978, J. Exp. Med., 148:223-234) revealed clear zones of lysis corresponding to molecular masses of 48 kD for urokinase-like PA and 75 kD for tissue PA, consistent with the molecular masses found for these enzymes in other tissues of the mouse (Danø, K., P. A. Andreasen, J. Grøndahl-Hansen, P. Kristensen, L. S. Nielsen, and L. Skriver, 1985, Adv. Cancer Res., 44:139-266). In other studies we have shown that PA-activated plasmin readily attacks critical adhesive basement membrane molecules. The present results indicate that enzymes involved in plasminogen activation, particularly urokinase-like PA, rapidly increase after axotomy, suggesting they may have a role early in muscle denervation. Similar alterations in PA activity might underlie the elimination of polyneuronal innervation during mammalian muscle development. Certain neuromuscular diseases may also involve activation of these enzymes, resulting in degradation of basement membrane zone components and, therefore, warrant further study.

scholarly journals Dysregulation of Muscle-Specific MicroRNAs as Common Pathogenic Feature Associated with Muscle Atrophy in ALS, SMA and SBMA: Evidence from Animal Models and Human Patients

2021 ◽  
Vol 22 (11) ◽  
pp. 5673
Author(s):  
Claudia Malacarne ◽  
Mariarita Galbiati ◽  
Eleonora Giagnorio ◽  
Paola Cavalcante ◽  
Franco Salerno ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Target Genes ◽  
Muscular Atrophy ◽  
Motor Neuron Diseases ◽  
Muscle Involvement ◽  
Mouse Muscle ◽  
Noninvasive Biomarkers ◽  
Muscle Impairment

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Due to the key role of muscle-specific microRNAs (myomiRs) in skeletal muscle development, by real-time PCR we investigated the expression of miR-206, miR-133a, miR-133b, and miR-1, and their target genes, in G93A-SOD1 ALS, Δ7SMA, and KI-SBMA mouse muscle during disease progression. Further, we analyzed their expression in serum of SOD1-mutated ALS, SMA, and SBMA patients, to demonstrate myomiR role as noninvasive biomarkers. Our data showed a dysregulation of myomiRs and their targets, in ALS, SMA, and SBMA mice, revealing a common pathogenic feature associated with muscle impairment. A similar myomiR signature was observed in patients’ sera. In particular, an up-regulation of miR-206 was identified in both mouse muscle and serum of human patients. Our overall findings highlight the role of myomiRs as promising biomarkers in ALS, SMA, and SBMA. Further investigations are needed to explore the potential of myomiRs as therapeutic targets for MND treatment.

scholarly journals Maternal methionine supplementation during gestation alters alternative splicing and DNA methylation in bovine skeletal muscle

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lihe Liu ◽  
Rocío Amorín ◽  
Philipe Moriel ◽  
Nicolás DiLorenzo ◽  
Phillip A. Lancaster ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alternative Splicing ◽  
Rna Splicing ◽  
Muscle Development ◽  
Maternal Nutrition ◽  
Muscle Physiology ◽  
Methyl Donors ◽  
Methionine Supplementation ◽  
Exon Usage ◽  
Isoform Expression

Abstract Background The evaluation of alternative splicing, including differential isoform expression and differential exon usage, can provide some insights on the transcriptional changes that occur in response to environmental perturbations. Maternal nutrition is considered a major intrauterine regulator of fetal developmental programming. The objective of this study was to assess potential changes in splicing events in the longissimus dorsi muscle of beef calves gestated under control or methionine-rich diets. RNA sequencing and whole-genome bisulfite sequencing were used to evaluate muscle transcriptome and methylome, respectively. Results Alternative splicing patterns were significantly altered by maternal methionine supplementation. Most of the altered genes were directly implicated in muscle development, muscle physiology, ATP activities, RNA splicing and DNA methylation, among other functions. Interestingly, there was a significant association between DNA methylation and differential exon usage. Indeed, among the set of genes that showed differential exon usage, significant differences in methylation level were detected between significant and non-significant exons, and between contiguous and non-contiguous introns to significant exons. Conclusions Overall, our findings provide evidence that a prenatal diet rich in methyl donors can significantly alter the offspring transcriptome, including changes in isoform expression and exon usage, and some of these changes are mediated by changes in DNA methylation.

scholarly journals Molecular Profiling of DNA Methylation and Alternative Splicing of Genes in Skeletal Muscle of Obese Rabbits

2021 ◽  
Vol 43 (3) ◽  
pp. 1558-1575
Author(s):  
Yanhong Li ◽  
Jie Wang ◽  
Mauricio A. Elzo ◽  
Huimei Fan ◽  
Kun Du ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Alternative Splicing ◽  
Genetic Modification ◽  
Muscle Development ◽  
Differential Methylation ◽  
Body Region ◽  
Messenger Rnas ◽  
Gene Body ◽  
Body Regions

DNA methylation and the alternative splicing of precursor messenger RNAs (pre-mRNAs) are two important genetic modification mechanisms. However, both are currently uncharacterized in the muscle metabolism of rabbits. Thus, we constructed the Tianfu black rabbit obesity model (obese rabbits fed with a 10% high-fat diet and control rabbits from 35 days to 70 days) and collected the skeletal muscle samples from the two groups for Genome methylation sequencing and RNA sequencing. DNA methylation data showed that the promoter regions of 599 genes and gene body region of 2522 genes had significantly differential methylation rates between the two groups, of which 288 genes had differential methylation rates in promoter and gene body regions. Analysis of alternative splicing showed 555 genes involved in exon skipping (ES) patterns, and 15 genes existed in differential methylation regions. Network analysis showed that 20 hub genes were associated with ubiquitinated protein degradation, muscle development pathways, and skeletal muscle energy metabolism. Our findings suggest that the two types of genetic modification have potential regulatory effects on skeletal muscle development and provide a basis for further mechanistic studies in the rabbit.

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