ArticleHuman molecular genetics2014
Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- RNA splicing and cardiovascular disease: a guide for cardiologists.European heart journal · 2026Review
- SAM68 is a multifunctional post-transcriptional regulator of cardiomyocyte differentiation.Nucleic acids research · 2026Article
- Alternative splicing of the Snap23 microexon is regulated by MBNL, QKI, and RBFOX2 in a tissue-specific manner and is altered in striated muscle diseases.RNA biology · 2025Article
- Decoding Cardiac Maturation Program: Insights from RNA Splicing Regulation.Current cardiology reports · 2025Review
- Molecular Regulation of Cardiomyocyte Maturation.Current cardiology reports · 2025Review
- Alternative Splicing in the Heart: The Therapeutic Potential of Regulating the Regulators.International journal of molecular sciences · 2024Review
- From gene-discovery to gene-tailored clinical management: 25 years of research in channelopathies and cardiomyopathies.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
- Myocardial Inflammation as a Manifestation of Genetic Cardiomyopathies: From Bedside to the Bench.Biomolecules · 2023Review
- Dilated cardiomyopathy caused by a pathogenic nucleotide variant in RBM20 in an Iranian family.BMC medical genomics · 2022Article
- Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies.Nature communications · 2021Article
- RBM20-Related Cardiomyopathy: Current Understanding and Future Options.Journal of clinical medicine · 2021Review
- Article
- RBM20 mutation and ventricular arrhythmias in a young patient with dilated cardiomyopathy: a case report.American journal of cardiovascular disease · 2021Article
- CaMKIIδ Splice Variants in the Healthy and Diseased Heart.Frontiers in cell and developmental biology · 2021Review
- New Insights in RBM20 Cardiomyopathy.Current heart failure reports · 2020Review
- iPSC Modeling of RBM20-Deficient DCM Identifies Upregulation of RBM20 as a Therapeutic Strategy.Cell reports · 2020Article
- Structural basis of UCUU RNA motif recognition by splicing factor RBM20.Nucleic acids research · 2020Article
- Cardiomyocyte Maturation: New Phase in Development.Circulation research · 2020Review
- Review
- RBM20 Regulates CaV1.2 Surface Expression by Promoting Exon 9* Inclusion ofInternational journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the underlying basis of cellular and molecular dysfunction is undetermined. Modeling human genetics using a high-throughput pluripotent stem cell platform was herein designed to pinpoint the initial transcriptome dysfunction and mechanistic corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic phenotype during cardiac differentiation. Intracellular Ca(2+) transients revealed Rbm20-dependent alteration in Ca(2+) handling, coinciding with known pathological splice variants of Titin and Camk2d genes by Day 24 of cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12 identified Rbm20-dependent dysregulation with 76% of differentially expressed genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream consequences of Rbm20-depletion at Day 24 of differentiation demonstrated significant dysregulation of extracellular matrix components such as the anomalous overexpression of the Vtn gene. By using the pluripotent stem cell platform to model human cardiac disease according to a stage-specific cardiogenic roadmap, we established a new paradigm of familial DCM pathogenesis as a developmental disorder that is patterned during early cardiogenesis and propagated with cellular mechanisms of pathological cardiac remodeling.
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