Abstract
Heart failure is one of the devastating public health problems with high mortality. Among various contributing factors for heart failure, severe dilated cardiomyopathy is the most common indication for cardiac transplantation. Recent evidence revealed that RBM20 mutation represents one main cause for familial dilated cardiomyopathy with a 3% prevalence in all forms of dilated cardiomyopathy. Further scrutiny of molecular mechanisms suggests a role for RBM20 as a functional splicing factor for protein isoform transition, indicating the clinical value of RBM20 mutations in the diagnosis and treatment of heart diseases. RBM20 alternatively splices a set of genes including titin, CaMKIID, and GIT2 at the post transcriptional level to yield diverse isoforms. These target proteins are necessary for cardiac homeostasis including structure and signal transduction. Mutations in RBM20 cause dilated cardiomyopathy along with dysregulated isoform switch. This review aims to summarize the current knowledge of RBM20-related dilated cardiomyopathy and heart failure as well as the underlying mechanism. We will emphasize and thoroughly discuss two splicing targets including titin and CaMKII which are known to play a vital role in dilated cardiomyopathy and heart failure.
Keywords: RBM20, heart failure, dilated cardiomyopathy, alternative splicing, titin, CaMKII.
Current Pharmaceutical Design
Title:Emerging Role for RBM20 and its Splicing Substrates in Cardiac Function and Heart Failure
Volume: 22 Issue: 31
Author(s): Jipeng Ma, Linhe Lu, Wei Guo, Jun Ren and Jian Yang
Affiliation:
Keywords: RBM20, heart failure, dilated cardiomyopathy, alternative splicing, titin, CaMKII.
Abstract: Heart failure is one of the devastating public health problems with high mortality. Among various contributing factors for heart failure, severe dilated cardiomyopathy is the most common indication for cardiac transplantation. Recent evidence revealed that RBM20 mutation represents one main cause for familial dilated cardiomyopathy with a 3% prevalence in all forms of dilated cardiomyopathy. Further scrutiny of molecular mechanisms suggests a role for RBM20 as a functional splicing factor for protein isoform transition, indicating the clinical value of RBM20 mutations in the diagnosis and treatment of heart diseases. RBM20 alternatively splices a set of genes including titin, CaMKIID, and GIT2 at the post transcriptional level to yield diverse isoforms. These target proteins are necessary for cardiac homeostasis including structure and signal transduction. Mutations in RBM20 cause dilated cardiomyopathy along with dysregulated isoform switch. This review aims to summarize the current knowledge of RBM20-related dilated cardiomyopathy and heart failure as well as the underlying mechanism. We will emphasize and thoroughly discuss two splicing targets including titin and CaMKII which are known to play a vital role in dilated cardiomyopathy and heart failure.
Export Options
About this article
Cite this article as:
Ma Jipeng, Lu Linhe, Guo Wei, Ren Jun and Yang Jian, Emerging Role for RBM20 and its Splicing Substrates in Cardiac Function and Heart Failure, Current Pharmaceutical Design 2016; 22 (31) . https://dx.doi.org/10.2174/1381612822666160701145322
DOI https://dx.doi.org/10.2174/1381612822666160701145322 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Do You See What I See: Recognition of Protozoan Parasites by Toll-Like Receptors
Current Immunology Reviews (Discontinued) Cardiac Oxidative Stress and Inflammatory Cytokines Response after Myocardial Infarction
Current Vascular Pharmacology Endothelial Dysfunction in Diabetes: From Mechanisms to Therapeutic Targets
Current Medicinal Chemistry Metabolomics and the Diagnosis of Human Diseases -A Guide to the Markers and Pathophysiological Pathways Affected
Current Medicinal Chemistry Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance
Current Cardiology Reviews Possible Therapeutic Targets in Cardiac Myocyte Apoptosis
Current Pharmaceutical Design Fatty Acids - Induced Lipotoxicity and Inflammation
Current Drug Metabolism Genetic and Non-genetic Determinants of Cardiovascular Disease in South Asians
Current Diabetes Reviews Cross-Talk Between Adipose Tissue Health, Myocardial Metabolism and Vascular Function: The Adipose-Myocardial and Adipose-Vascular Axes
Current Pharmaceutical Design The Emerging Roles of Leptin and Ghrelin in Cardiovascular Physiology and Pathophysiology
Current Vascular Pharmacology Toxicology of Trastuzumab: An Insight into Mechanisms of Cardiotoxicity
Current Cancer Drug Targets Cardiovascular Magnetic Resonance T2-weighted Imaging of Myocardial Edema in Acute Myocardial Infarction
Recent Patents on Cardiovascular Drug Discovery Fontan Circulation Might be Associated with Peripartum Cardiomyopathy: A Review of Mechanistic and Clinical Aspects
Current Cardiology Reviews Pathogenetic Pathways of Cardiorenal Syndrome and their Possible Therapeutic Implications
Current Pharmaceutical Design Current Advances in the Synthesis and Antitumoral Activity of SIRT1-2 Inhibitors by Modulation of p53 and Pro-Apoptotic Proteins
Current Medicinal Chemistry Novel Insights into Complex Cardiovascular Pathologies using 4D Flow Analysis by Cardiovascular Magnetic Resonance Imaging
Current Pharmaceutical Design Prognostic Utility of Troponin I and N Terminal-ProBNP among Patients with Heart Failure due to Non-Ischemic Cardiomyopathy and Important Correlations
Cardiovascular & Hematological Agents in Medicinal Chemistry The C-Reactive Protein Levels in Left Ventricular Dysfunction of Different Etiology
Inflammation & Allergy - Drug Targets (Discontinued) Auto-Antibodies As Possible Markers and Mediators of Ischemic, Dilated, and Rhythmic Cardiopathies
Current Drug Targets The Hepatic Lipidome: A Gateway to Understanding the Pathogenes is of Alcohol-Induced Fatty Liver
Current Molecular Pharmacology