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Updated: Jun 19, 2026
In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes
Published on: June 22, 2020
Rbm20 ablation is associated with changes in the expression of titin-interacting and metabolic proteins
Eli J Larson1, Zachery R Gregorich2, Yanghai Zhang2
1Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
Abstract:
Dilated cardiomyopathy (DCM) is a major risk factor for developing heart failure and is often associated with an increased risk for life-threatening arrhythmia. Although numerous causal genes for DCM have been identified, RNA binding motif protein 20 (Rbm20) remains one of the few splicing factors that, when mutated or genetically ablated, leads to the development of DCM. In this study we sought to identify changes in the cardiac proteome in Rbm20 knockout (KO) rat hearts using global quantitative proteomics to gain insight into the molecular mechanisms precipitating the development of DCM in these rats. Our analysis identified changes in titin-interacting proteins involved in mechanical stretch-based signaling, as well as mitochondrial enzymes, which suggests that activation of pathological hypertrophy and altered mitochondrial metabolism and/or dysfunction, among other changes, contribute to the development of DCM in Rbm20 KO rats. Collectively, our findings provide the first report on changes in the cardiac proteome associated with genetic ablation of Rbm20.
Insights
Genetic ablation of RNA binding motif protein 20 (Rbm20) causes dilated cardiomyopathy (DCM) in rats. Proteomic analysis revealed altered titin interactions and mitochondrial metabolism, contributing to DCM development.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Proteomics
Background:
- Dilated cardiomyopathy (DCM) is a leading cause of heart failure and arrhythmia.
- Mutations in RNA binding motif protein 20 (Rbm20) are linked to DCM.
- The precise molecular mechanisms underlying Rbm20-associated DCM are not fully understood.
Purpose of the Study:
- To investigate the cardiac proteomic changes in Rbm20 knockout (KO) rat hearts.
- To elucidate the molecular pathways contributing to DCM development in the absence of Rbm20.
Main Methods:
- Global quantitative proteomics was employed on cardiac tissue from Rbm20 KO rats.
- Comparative proteomic analysis was performed to identify differentially expressed proteins.
Main Results:
- Significant alterations were observed in titin-interacting proteins, suggesting impaired mechanical stretch signaling.
- Changes in mitochondrial enzymes indicate altered mitochondrial metabolism and potential dysfunction.
- These proteomic shifts provide insights into pathological hypertrophy and metabolic dysregulation in Rbm20 KO hearts.
Conclusions:
- Genetic ablation of Rbm20 leads to DCM through complex molecular alterations.
- The study highlights the role of titin interactions and mitochondrial function in Rbm20-mediated cardiac pathology.
- This is the first report detailing cardiac proteome changes associated with Rbm20 deficiency.
