Alternative splicing is the main driver of protein diversity and allows the production of different proteins from each gene in the genome. Changes in exon exclusion, intron retention or the use of alternative splice sites can alter protein structure, localisation, regulation and function. In the heart, alternative splicing of sarcomeric genes, ion channels and cell signalling proteins can lead to cardiomyopathies, arrhythmias and other pathologies. Also, a number of inherited conditions and heart-related diseases develop as a result of mutations affecting splicing. Here, we review the impact that changes in alternative splicing have on individual genes and on whole biological processes associated with heart disease. We also discuss promising therapeutic tools based on the manipulation of alternative splicing.
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hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function
Molecular identification of the dominant-negative, splicing isoform of the two-pore domain K(+) channel K(2P)5.1 in lymphoid cells and enhancement of its expression by splicing inhibition
Novel Kidins220/ARMS Splice Isoforms: Potential Specific Regulators of Neuronal and Cardiovascular Development
Intronic deletions of tva receptor gene decrease the susceptibility to infection by avian sarcoma and leukosis virus subgroup A
FineSplice, enhanced splice junction detection and quantification: a novel pipeline based on the assessment of diverse RNA-Seq alignment solutions
Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems
RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to Disturbed Calcium Handling
Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease
Association of intronic DNA methylation and hydroxymethylation alterations in the epigenetic etiology of dilated cardiomyopathy
Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms
Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant
RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy
The Emerging Role of the RBM20 and PTBP1 Ribonucleoproteins in Heart Development and Cardiovascular Diseases
Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators
Angiotensin II Influences Pre-mRNA Splicing Regulation by Enhancing RBM20 Transcription Through Activation of the MAPK/ELK1 Signaling Pathway
Modeling epistasis in mice and yeast using the proportion of two or more distinct genetic backgrounds: Evidence for "polygenic epistasis"
Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy
Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy
Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere
Alternatively spliced IS6 segments of the alpha 1C gene determine the tissue-specific dihydropyridine sensitivity of cardiac and vascular smooth muscle L-type Ca2+ channels
A truncated cardiac troponin T molecule in transgenic mice suggests multiple cellular mechanisms for familial hypertrophic cardiomyopathy
Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188
Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle
Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
Replacement of the muscle-specific sarcoplasmic reticulum Ca(2+)-ATPase isoform SERCA2a by the nonmuscle SERCA2b homologue causes mild concentric hypertrophy and impairs contraction-relaxation of the heart
Increased expression of alternatively spliced dominant-negative isoform of SRF in human failing hearts
Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice
Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms
Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium
Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts
ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle
Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome
Alternative pre-mRNA splicing governs expression of a conserved acidic transactivation domain in myocyte enhancer factor 2 factors of striated muscle and brain
Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes
Alternative splicing of ryanodine receptors modulates cardiomyocyte Ca2+ signaling and susceptibility to apoptosis
Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy
Human heart failure is associated with abnormal C-terminal splicing variants in the cardiac sodium channel
Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation
A naturally occurring calcineurin variant inhibits FoxO activity and enhances skeletal muscle regeneration
Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation
Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.
CREs: Gene & Cell Therapy
Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.
Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.
Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.
Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.