GO:0060299 negative regulation of sarcomere organization: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0060299 (negative regulation of sarcomere organization) describes any process that decreases the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres.
• Sarcomere organization is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs.
• Negative regulation of sarcomere organization is critical for proper muscle development, function, and regeneration, and its dysregulation is linked to neuromuscular disorders and cardiac dysfunction [1,5].
• Key molecular players include sarcomeric proteins (e.g., MYH7, ACTC1, TNNT2), signaling pathways (e.g., JAK/STAT, MRTF-SRF), and microRNAs (e.g., miR-221/222) [2,5,7].
• Experimental models such as knockout, point mutation, knock-in, and overexpression cell models are essential to dissect the causal role of genes in this process [2,5,7].
• EDITGENE provides comprehensive CRISPR services including knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics to study negative regulation of sarcomere organization [1,2,5].
Description
The Gene Ontology (GO) term GO:0060299, negative regulation of sarcomere organization, is a biological process that encompasses any mechanism that decreases the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres. The sarcomere is the fundamental contractile unit of striated muscle, consisting of an array of overlapping thick and thin filaments anchored between two adjacent Z discs. Proper regulation of sarcomere organization is essential for muscle development, maintenance, and function, and its dysregulation contributes to a range of neuromuscular and cardiac disorders [1,5]. Understanding the negative regulation of sarcomere organization is therefore of significant interest to researchers in muscle biology, regenerative medicine, and disease modeling. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a comprehensive overview of the mechanisms, genes, and research methods associated with GO:0060299.
negative regulation of sarcomere organization At A Glance
| GO ID | GO:0060299 |
|---|---|
| GO term | negative regulation of sarcomere organization |
| Ontology | biological_process |
| Synonym | negative regulation of sarcomere organisation |
| Definition | Any process that decreases the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres. The sarcomere is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs. |
| Major function | Negative regulation of sarcomere assembly and organization |
| Related processes | Muscle contraction, myofibril assembly, sarcomere organization |
| Disease relevance | Neuromuscular disorders, cardiac dysfunction, muscle atrophy |
What Is GO:0060299?
GO:0060299, negative regulation of sarcomere organization, is defined as any process that decreases the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres. The sarcomere is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs. This term is a biological process and is also known by the synonym negative regulation of sarcomere organisation.
Why Is negative regulation of sarcomere organization Important in Cell Biology?
Negative regulation of sarcomere organization is crucial for maintaining muscle homeostasis and adapting to physiological demands. Dysregulation of this process can lead to impaired muscle contractility, as seen in neuromuscular disorders and cardiac pathologies [1,5]. For example, loss of sarcomeric proteins via upregulation of JAK/STAT signaling underlies interferon-γ-induced contractile deficit in engineered human myocardium. Understanding the negative regulators of sarcomere organization provides insights into disease mechanisms and potential therapeutic targets.
• Maintains muscle cell integrity by preventing excessive or aberrant sarcomere assembly.
• Regulates muscle development and regeneration through controlled myofibril organization.
• Its dysregulation is implicated in neuromuscular disorders such as satellite cell-opathies.
• Plays a role in cardiac dysfunction, including interferon-γ-induced contractile deficits.
• Involved in stress responses in skeletal muscle, as shown in rainbow trout transcriptomic studies.
• Modulated by microRNAs such as miR-221 and miR-222 during skeletal muscle differentiation.
• Affected by environmental factors like temperature, influencing muscle cell proliferation and differentiation.
• Targeted by signaling pathways such as JAK/STAT and MRTF-SRF [2,5].
• Provides potential therapeutic targets for muscle-wasting conditions and cardiomyopathies [1,5].
• Essential for understanding the molecular basis of muscle adaptation and disease [2,5].
What Happens During negative regulation of sarcomere organization?
Inhibition of Sarcomeric Protein Expression
In simple terms: This step reduces the production of proteins that build sarcomeres.
Negative regulation of sarcomere organization can occur through decreased expression of sarcomeric proteins. For instance, interferon-γ-induced upregulation of JAK/STAT signaling leads to loss of sarcomeric proteins and contractile deficit in engineered human myocardium. Similarly, microRNA-221 and microRNA-222 modulate differentiation and maturation of skeletal muscle cells, potentially by targeting sarcomeric components.
Disruption of Sarcomere Assembly
In simple terms: This step interferes with the physical assembly of sarcomere structures.
Processes that disrupt the ordered assembly of thick and thin filaments into sarcomeres negatively regulate sarcomere organization. For example, sulforaphane exposure impairs contractility and mitochondrial function in three-dimensional engineered heart tissue, likely by disrupting sarcomere assembly. Additionally, temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora may involve altered sarcomere organization.
Regulation by Signaling Pathways
In simple terms: This step involves cellular signals that turn down sarcomere building.
Signaling pathways such as MRTF-SRF and JAK/STAT are key regulators of sarcomere organization. Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling, and loss of sarcomeric proteins via JAK/STAT signaling underlies contractile deficits. These pathways can negatively regulate sarcomere organization by modulating gene expression.
Role of MicroRNAs
In simple terms: Small RNA molecules can fine-tune sarcomere formation.
MicroRNAs such as miR-221 and miR-222 modulate differentiation and maturation of skeletal muscle cells, and may negatively regulate sarcomere organization by targeting mRNAs encoding sarcomeric proteins or regulatory factors. Their precise role in this process is an active area of research.
Environmental and Stress Responses
In simple terms: External factors can reduce sarcomere organization.
Environmental stressors such as temperature changes and hormonal signals can negatively regulate sarcomere organization. For example, 11-deoxycorticosterone affects the transcriptomic response to stress in rainbow trout skeletal muscle, and temperature regulates proliferation and differentiation in skeletal muscle cells of Nibea albiflora. These responses may involve downregulation of sarcomere-related genes.
Key Genes Involved in GO:0060299 negative regulation of sarcomere organization
The following genes and proteins are key players in the negative regulation of sarcomere organization, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MYH7 | Thick filament component; mutations cause cardiomyopathy | Studied in sarcomere assembly and disease models |
| ACTC1 | Thin filament component; actin isoform in heart | Involved in sarcomere organization and contractility |
| TNNT2 | Thin filament regulatory protein; troponin T | Mutations linked to cardiac dysfunction |
| JAK/STAT | Signaling pathway that downregulates sarcomeric proteins | Mediates interferon-γ-induced contractile deficit |
| MRTF-SRF | Transcription factor pathway regulating sarcomere genes | Controls cardiomyocyte maturation |
| miR-221 | MicroRNA modulating muscle differentiation | Regulates skeletal muscle cell maturation |
| miR-222 | MicroRNA modulating muscle differentiation | Regulates skeletal muscle cell maturation |
| Rab1 | GTPase involved in ER-to-Golgi transport | Regulates cell surface expression of AT1 receptor in cardiac myocytes |
| AT1 receptor | Angiotensin II type 1 receptor | Regulated by Rab1 in cardiac myocytes |
| MYL2 | Regulatory light chain of myosin | Component of sarcomere; potential target |
| TNNI3 | Troponin I; inhibitory subunit | Regulates muscle contraction |
| TPM1 | Tropomyosin; thin filament protein | Involved in sarcomere organization |
| MYBPC3 | Myosin binding protein C | Modulates sarcomere assembly |
| ACTN2 | Alpha-actinin-2; Z-disc protein | Structural component of sarcomere |
| DES | Desmin; intermediate filament protein | Maintains sarcomere integrity |
| DMD | Dystrophin; links sarcomere to membrane | Mutations cause muscular dystrophy |
| SGCA | Sarcoglycan alpha; dystrophin-associated protein | Involved in muscle stability |
| LAMA2 | Laminin subunit alpha-2 | Extracellular matrix component affecting sarcomere |
How Is negative regulation of sarcomere organization Regulated?
The negative regulation of sarcomere organization is controlled by multiple signaling pathways and transcriptional regulators. The MRTF-SRF pathway regulates sarcomere gene expression and cardiomyocyte maturation. JAK/STAT signaling, when activated by interferon-γ, downregulates sarcomeric proteins and impairs contractility. MicroRNAs such as miR-221 and miR-222 fine-tune muscle differentiation and maturation. Additionally, environmental factors like temperature and hormones can modulate this process through transcriptomic changes [3,8].
negative regulation of sarcomere organization and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| JAK/STAT | Interferon-γ-induced contractile deficit | Engineered human myocardium |
| MYH7 | Cardiomyopathy | Knockout or point mutation in cardiomyocytes |
| DMD | Duchenne muscular dystrophy | Knockout mouse or patient-derived iPSCs |
| miR-221/222 | Muscle differentiation disorders | Overexpression in skeletal muscle cells |
| LAMA2 | Congenital muscular dystrophy | Knockout zebrafish or mouse |
Neuromuscular Disorders
Dysregulation of negative regulation of sarcomere organization contributes to neuromuscular disorders. Muscle satellite cell dysfunction is involved in neuromuscular disorders, expanding the portfolio of satellite cell-opathies. Impaired sarcomere organization can lead to muscle weakness and wasting.
Cardiac Dysfunction
In cardiac muscle, loss of sarcomeric proteins via upregulation of JAK/STAT signaling underlies interferon-γ-induced contractile deficit in engineered human myocardium. This highlights the importance of negative regulation in maintaining cardiac function.
Muscle Atrophy and Stress Responses
Environmental stressors and hormonal signals can negatively regulate sarcomere organization, as seen in rainbow trout skeletal muscle exposed to 11-deoxycorticosterone. Temperature also regulates proliferation and differentiation in skeletal muscle cells of Nibea albiflora, suggesting a role in muscle adaptation.
From negative regulation of sarcomere organization-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X negatively regulate sarcomere organization? | Knockout cell model (e.g., CRISPR-Cas9) |
| Does a specific mutation in gene Y affect sarcomere assembly? | Point mutation knock-in cell model |
| How does tagging gene Z affect its function in sarcomeres? | Tagged knock-in (e.g., GFP) |
| What is the effect of overexpressing gene W on sarcomere organization? | Overexpression cell model |
| Which genes are involved in negative regulation? | CRISPR library screening |
| What are the transcriptomic changes during negative regulation? | RNA-seq in knockout vs wild-type |
How to Study the negative regulation of sarcomere organization Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify pathways in negative regulation [3,8] |
| Proteomics | Protein abundance and modifications | Quantify sarcomeric protein loss |
| Immunofluorescence | Sarcomere structure and localization | Visualize sarcomere organization |
| Contractility assay | Muscle contraction force | Assess functional impact [5,6] |
| CRISPR screening | Gene function at scale | Discover novel regulators |
| Bioinformatics | Pathway and network analysis | Interpret omics data [1,3] |
| Western blot | Specific protein levels | Validate knockout or overexpression |
| qPCR | mRNA expression | Confirm gene expression changes |
Transcriptomic Analysis
RNA-seq can identify global changes in gene expression during negative regulation of sarcomere organization. For example, transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora revealed key pathways. Similarly, the transcriptomic response to stress in rainbow trout skeletal muscle was studied using RNA-seq.
Proteomic and Imaging Approaches
Proteomics and immunofluorescence imaging can quantify sarcomeric protein levels and organization. Loss of sarcomeric proteins via JAK/STAT signaling was demonstrated in engineered human myocardium using these methods. High-content imaging can assess sarcomere structure in knockout or overexpression models.
Functional Contractility Assays
Engineered heart tissue and cardiomyocyte contractility assays measure the functional consequences of negative regulation. Sulforaphane exposure impaired contractility in three-dimensional engineered heart tissue, and interferon-γ-induced contractile deficit was assessed in engineered human myocardium.
CRISPR Screening and Bioinformatics
CRISPR library screening combined with bioinformatics can identify novel regulators of sarcomere organization. This approach enables unbiased discovery of genes that negatively regulate sarcomere assembly, as highlighted in studies of muscle satellite cell dysfunction.
How CRISPR Can Be Used to Study GO:0060299 negative regulation of sarcomere organization
Knockout
CRISPR knockout cell models are used to eliminate candidate genes and assess their role in negative regulation of sarcomere organization. For example, knocking out JAK/STAT components can prevent interferon-γ-induced loss of sarcomeric proteins. Knockout of sarcomeric genes themselves can reveal their necessity for sarcomere assembly.
Point Mutation
Point mutation knock-in models introduce specific disease-associated mutations to study their impact on sarcomere organization. For instance, mutations in MYH7 or TNNT2 can be modeled to understand how they affect sarcomere function and regulation.
Knock-in
Tagged knock-in models (e.g., GFP fusion) allow real-time visualization of sarcomeric proteins and their dynamics during negative regulation. This approach can track protein localization and turnover in live cells.
Overexpression
Overexpression models drive high levels of a candidate gene to test whether it negatively regulates sarcomere organization. For example, overexpressing miR-221/222 in skeletal muscle cells can modulate differentiation and maturation. Overexpression of signaling components like JAK/STAT can mimic contractile deficits.
How EDITGENE Supports negative regulation of sarcomere organization Research
Researchers studying negative regulation of sarcomere organization-related genes often need to determine whether a candidate gene is causally involved in this process. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such investigations, from gene knockout to precise point mutations and overexpression.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of sarcomere organization research.
Frequently Asked Questions About negative regulation of sarcomere organization
What is GO:0060299?
GO:0060299 is the Gene Ontology term for negative regulation of sarcomere organization, defined as any process that decreases the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres.
What genes are involved in negative regulation of sarcomere organization?
Key genes include MYH7, ACTC1, TNNT2, JAK/STAT pathway components, MRTF-SRF, and microRNAs such as miR-221 and miR-222 [2,5,7].
How is sarcomere organization negatively regulated?
It is negatively regulated by signaling pathways like JAK/STAT and MRTF-SRF, microRNAs, and environmental factors that reduce sarcomeric protein expression or disrupt assembly [2,5,7].
What diseases are associated with dysregulation of sarcomere organization?
Neuromuscular disorders, cardiomyopathies, and muscle atrophy are associated with dysregulation of sarcomere organization [1,5].
What experimental models are used to study negative regulation of sarcomere organization?
Knockout, point mutation, knock-in, and overexpression cell models, as well as CRISPR library screening, are commonly used [2,5,7].
How can CRISPR be used to study GO:0060299?
CRISPR can create knockout, point mutation, knock-in, and overexpression models to test the causal role of specific genes in negative regulation of sarcomere organization [2,5].
What is the role of JAK/STAT signaling in sarcomere organization?
JAK/STAT signaling, when activated by interferon-γ, downregulates sarcomeric proteins and impairs contractility, thus negatively regulating sarcomere organization.
What is the role of microRNAs in sarcomere organization?
MicroRNAs such as miR-221 and miR-222 modulate skeletal muscle cell differentiation and maturation, potentially by targeting sarcomeric genes.
How does temperature affect sarcomere organization?
Temperature regulates proliferation and differentiation in skeletal muscle cells, which may involve changes in sarcomere organization.
What services does EDITGENE offer for studying negative regulation of sarcomere organization?
EDITGENE offers knockout, point mutation, knock-in, overexpression cell models, CRISPR library screening, and bioinformatics services [1,2,5].
Conclusion
GO:0060299, negative regulation of sarcomere organization, is a critical biological process that ensures proper muscle function by controlling the assembly of sarcomeres. Dysregulation of this process is linked to neuromuscular disorders and cardiac dysfunction, making it a key area of research. With the aid of CRISPR-based models and advanced bioinformatics, researchers can dissect the molecular mechanisms and identify therapeutic targets. EDITGENE provides comprehensive services to support these investigations, from gene knockout to library screening.
References
- 1. Ganassi M et al.. 2022. Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.. Eur J Transl Myol 32(1) PMID: 35302338
- 2. Guo Y et al.. 2021. Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling.. Proc Natl Acad Sci U S A 118(2) PMID: 33361330
- 3. Zuloaga R et al.. 2023. Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle.. Genes (Basel) 14(2) PMID: 36833439
- 4. Filipeanu CM et al.. 2004. Regulation of the cell surface expression and function of angiotensin II type 1 receptor by Rab1-mediated endoplasmic reticulum-to-Golgi transport in cardiac myocytes.. J Biol Chem 279(39):41077-84 PMID: 15252015
- 5. Zhan RZ et al.. 2021. Loss of sarcomeric proteins via upregulation of JAK/STAT signaling underlies interferon-γ-induced contractile deficit in engineered human myocardium.. Acta Biomater 126:144-153 PMID: 33705988
- 6. Rhoden A et al.. 2021. Sulforaphane exposure impairs contractility and mitochondrial function in three-dimensional engineered heart tissue.. Redox Biol 41:101951 PMID: 33831709
- 7. Cardinali B et al.. 2009. Microrna-221 and microrna-222 modulate differentiation and maturation of skeletal muscle cells.. PLoS One 4(10):e7607 PMID: 19859555
- 8. Zhang J et al.. 2026. Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.. Comp Biochem Physiol Part D Genomics Proteomics 60:101911 PMID: 42330807
