ArticleBasic research in cardiology2022
Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs.
Article in Basic research in cardiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- The emerging roles of small nucleolar RNAs, piwi-interacting RNAs, tRNA-derived small RNAs, and circular RNAs in the regulation of cardiac hypertrophy, ischemic heart disease, and heart failure.Genes & diseases · 2026Review
- Circular RNAs in Cardiovascular Diseases: From Regulatory Networks to Functional Effectors.International journal of molecular sciences · 2026Review
- Integrated heart-blood RNA editome profiling reveals circulating A-to-I editing candidates linked to dilated cardiomyopathy myocardial signatures and heart failure.Journal of molecular and cellular cardiology plus · 2026Article
- RNA editing in cardiovascular health and disease.Communications biology · 2026Review
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- Advances in RNA modification in myocardial fibrosis (Review).International journal of molecular medicine · 2025Review
- circRNA/TLR interaction: key players in immune regulation and autoimmune diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Circulating Immune Cell Signature Analysis in HFpEF Across Species.Circulation research · 2025Article
- Global dysregulation of circular RNAs in frontal cortex and whole blood from DM1 and DM2.Human genetics · 2025Article
- Circular RNA Formation and Degradation Are Not Directed by Universal Pathways.International journal of molecular sciences · 2025Review
- Methylations in dilated cardiomyopathy and heart failure.Frontiers in cardiovascular medicine · 2025Review
- Formation of Circular RNAs.Advances in experimental medicine and biology · 2025Review
- RNA modifications in cancer.MedComm · 2025Review
- Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease.Nature reviews. Cardiology · 2024Review
- RNA editing regulates glutamatergic synapses in the frontal cortex of a molecular subtype of Amyotrophic Lateral Sclerosis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Circular RNAs: a small piece in the heart failure puzzle.Functional & integrative genomics · 2024Review
- Epitranscriptomic Regulations in the Heart.Physiological research · 2024Review
- Recommendations for detection, validation, and evaluation of RNA editing events in cardiovascular and neurological/neurodegenerative diseases.Molecular therapy. Nucleic acids · 2024Review
- Early-stage idiopathic Parkinson's disease is associated with reduced circular RNA expression.NPJ Parkinson's disease · 2024Article
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Authors and funding
20 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alterations of RNA editing that affect the secondary structure of RNAs can cause human diseases. We therefore studied RNA editing in failing human hearts. Transcriptome sequencing showed that adenosine-to-inosine (A-to-I) RNA editing was responsible for 80% of the editing events in the myocardium. Failing human hearts were characterized by reduced RNA editing. This was primarily attributable to Alu elements in introns of protein-coding genes. In the failing left ventricle, 166 circRNAs were upregulated and 7 circRNAs were downregulated compared to non-failing controls. Most of the upregulated circRNAs were associated with reduced RNA editing in the host gene. ADAR2, which binds to RNA regions that are edited from A-to-I, was decreased in failing human hearts. In vitro, reduction of ADAR2 increased circRNA levels suggesting a causal effect of reduced ADAR2 levels on increased circRNAs in the failing human heart. To gain mechanistic insight, one of the identified upregulated circRNAs with a high reduction of editing in heart failure, AKAP13, was further characterized. ADAR2 reduced the formation of double-stranded structures in AKAP13 pre-mRNA, thereby reducing the stability of Alu elements and the circularization of the resulting circRNA. Overexpression of circAKAP13 impaired the sarcomere regularity of human induced pluripotent stem cell-derived cardiomyocytes. These data show that ADAR2 mediates A-to-I RNA editing in the human heart. A-to-I RNA editing represses the formation of dsRNA structures of Alu elements favoring canonical linear mRNA splicing and inhibiting the formation of circRNAs. The findings are relevant to diseases with reduced RNA editing and increased circRNA levels and provide insights into the human-specific regulation of circRNA formation.
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