ArticleHeart rhythm2018
HuR-mediated SCN5A messenger RNA stability reduces arrhythmic risk in heart failure.
Article in Heart rhythm, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Cardiac Sodium Channel Regulation: A Potential New Therapeutic Target in Cardiomyopathy.Circulation research · 2026Article
- Sodium Channel mRNA Binding Proteins.JACC. Basic to translational science · 2026Article
- Stress-Induced Down-Regulation of CPEB4 Disrupts Sodium Channel Regulation and Myocardial Excitability.JACC. Basic to translational science · 2026Article
- Structural, biological, and biomedical implications of mRNA interactions with the master regulator HuR.NAR molecular medicine · 2025Review
- YTHDF1 is pivotal for maintenance of cardiac homeostasis.Journal of molecular and cellular cardiology · 2024Article
- Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review.Biomedicines · 2024Review
- Knockdown of SCN5A alters metabolic-associated genes and aggravates hypertrophy in the cardiomyoblast.Molecular biology reports · 2024Article
- RNA binding proteins as mediators of pathological cardiac remodeling.Frontiers in cell and developmental biology · 2024Review
- miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure.Heart rhythm · 2023Article
- Comprehensive review on gene mutations contributing to dilated cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
- Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.Trends in molecular medicine · 2022Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Landscape of RNA-binding proteins in diagnostic utility, immune cell infiltration and PANoptosis features of heart failure.Frontiers in genetics · 2022Article
- HuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes.JCI insight · 2021Article
- Inhibition of the unfolded protein response reduces arrhythmia risk after myocardial infarction.The Journal of clinical investigation · 2021Article
- MIR448 antagomir reduces arrhythmic risk after myocardial infarction by upregulating the cardiac sodium channel.JCI insight · 2020Article
- LINC00205 promotes malignancy in lung cancer by recruiting FUS and stabilizing CSDE1.Bioscience reports · 2020Article
- mRNA Metabolism in Cardiac Development and Disease: Life After Transcription.Physiological reviews · 2020Review
- Life Cycle of the Cardiac Voltage-Gated Sodium Channel NaFrontiers in physiology · 2020Review
- Cardiovascular inflammation: RNA takes the lead.Journal of molecular and cellular cardiology · 2019Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundDownregulated sodium currents in heart failure (HF) have been linked to increased arrhythmic risk. Reduced expression of the messenger RNA (mRNA)-stabilizing protein HuR (also known as ELAVL1) may be responsible for the downregulation of sodium channel gene SCN5A mRNA.
objectiveThe purpose of this article was to investigate whether HuR regulates SCN5A mRNA expression and whether manipulation of HuR benefits arrhythmia control in HF.
methodsQuantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of SCN5A. Optical mapping of the intact heart was adopted to study the effects of HuR on the conduction velocity and action potential upstroke in mice with myocardial infarct and HF after injection of AAV9 viral particles carrying HuR.
resultsHuR was associated with SCN5A mRNA in cardiomyocytes, and expression of HuR was downregulated in failing hearts. The association of HuR and SCN5A mRNA protected SCN5A mRNA from decay. Injection of AAV9 viral particles carrying HuR increased SCN5A expression in mouse heart tissues after MI. Optical mapping of the intact heart demonstrated that overexpression of HuR improved action potential upstroke and conduction velocity in the infarct border zone, which reduced the risk of reentrant arrhythmia after MI.
conclusionOur data indicate that HuR is an important RNA-binding protein in maintaining SCN5A mRNA abundance in cardiomyocytes. Reduced expression of HuR may be at least partially responsible for the downregulation of SCN5A mRNA expression in ischemic HF. Overexpression of HuR may rescue decreased SCN5A expression and reduce arrhythmic risk in HF. Increasing mRNA stability to increase ion channel currents may correct a fundamental defect in HF and represent a new paradigm in antiarrhythmic therapy.
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