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Article

Deep Characterization of Circular RNAs from Human Cardiovascular Cell Models and Cardiac Tissue

1
Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany
2
Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, 69120 Heidelberg, Germany
3
German Centre for Cardiovascular Research (DZHK)-Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
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Institute of Experimental Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany
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Institute for Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany
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German Centre for Cardiovascular Research (DZHK)-Partner site Rhine/Main, 60590 Frankfurt, Germany
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(7), 1616; https://doi.org/10.3390/cells9071616
Received: 16 May 2020 / Revised: 25 June 2020 / Accepted: 26 June 2020 / Published: 4 July 2020
(This article belongs to the Special Issue Circular RNAs: Non-canonical Observations on Non-canonical RNAs)
For decades, cardiovascular disease (CVD) has been the leading cause of death throughout most developed countries. Several studies relate RNA splicing, and more recently also circular RNAs (circRNAs), to CVD. CircRNAs originate from linear transcripts and have been shown to exhibit tissue-specific expression profiles. Here, we present an in-depth analysis of sequence, structure, modification, and cardiac circRNA interactions. We used human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs), human healthy and diseased (ischemic cardiomyopathy, dilated cardiomyopathy) cardiac tissue, and human umbilical vein endothelial cells (HUVECs) to profile circRNAs. We identified shared circRNAs across all samples, as well as model-specific circRNA signatures. Based on these circRNAs, we identified 63 positionally conserved and expressed circRNAs in human, pig, and mouse hearts. Furthermore, we found that the sequence of circRNAs can deviate from the sequence derived from the genome sequence, an important factor in assessing potential functions. Integration of additional data yielded evidence for m6A-methylation of circRNAs, potentially linked to translation, as well as, circRNAs overlapping with potential Argonaute 2 binding sites, indicating potential association with the RISC complex. Moreover, we describe, for the first time in cardiac model systems, a sub class of circRNAs containing the start codon of their primary transcript (AUG circRNAs) and observe an enrichment for m6A-methylation for AUG circRNAs. View Full-Text
Keywords: circRNAs; hiPSC-CMs; HUVEC; AUG circRNAs; RNase R; conservation; m6A-methylation circRNAs; hiPSC-CMs; HUVEC; AUG circRNAs; RNase R; conservation; m6A-methylation
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MDPI and ACS Style

Jakobi, T.; Siede, D.; Eschenbach, J.; Heumüller, A.W.; Busch, M.; Nietsch, R.; Meder, B.; Most, P.; Dimmeler, S.; Backs, J.; Katus, H.A.; Dieterich, C. Deep Characterization of Circular RNAs from Human Cardiovascular Cell Models and Cardiac Tissue. Cells 2020, 9, 1616. https://doi.org/10.3390/cells9071616

AMA Style

Jakobi T, Siede D, Eschenbach J, Heumüller AW, Busch M, Nietsch R, Meder B, Most P, Dimmeler S, Backs J, Katus HA, Dieterich C. Deep Characterization of Circular RNAs from Human Cardiovascular Cell Models and Cardiac Tissue. Cells. 2020; 9(7):1616. https://doi.org/10.3390/cells9071616

Chicago/Turabian Style

Jakobi, Tobias, Dominik Siede, Jessica Eschenbach, Andreas W. Heumüller, Martin Busch, Rouven Nietsch, Benjamin Meder, Patrick Most, Stefanie Dimmeler, Johannes Backs, Hugo A. Katus, and Christoph Dieterich. 2020. "Deep Characterization of Circular RNAs from Human Cardiovascular Cell Models and Cardiac Tissue" Cells 9, no. 7: 1616. https://doi.org/10.3390/cells9071616

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