Universität zu Köln

Siede, D., Rapti, K., Gorska, A. A., Katus, H. A., Altmueller, J., Boeckel, J. N., Meder, B., Maack, C., Voelkers, M., Mueller, O. J., Backs, J. and Dieterich, C. (2017). Identification of circular RNAs with host gene-independent expression in human model systems for cardiac differentiation and disease. J. Mol. Cell. Cardiol., 109. S. 48 - 57. OXFORD: ELSEVIER SCI LTD. ISSN 1095-8584

Full text not available from this repository.

Abstract

Aims: Cardiovascular disease, one of the most common causes of death in western populations, is characterized by changes in RNA splicing and expression. Circular RNAs (circRNA) originate from back-splicing events, which link a downstream 5' splice site to an upstream 3' splice site. Several back-splicing junctions (BSJ) have been described in heart biopsies from human, rat and mouse hearts (Werfel et al., 2016; Jakobi et al., 2016). Here, we use human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to identify circRNA and host gene dynamics in cardiac development and disease. In parallel, we explore candidate interactions of selected homologs in mouse and rat via RIP-seq experiments. Methods and Results: Deep RNA sequencing of cardiomyocyte development and beta-adrenergic stimulation uncovered 4518 circRNAs. The set of circular RNA host genes is enriched for chromatin modifiers and GTPase activity regulators. RNA-seq and qRT-PCR data showed that circular RNA expression is highly dynamic in the hiPSC-CM model with 320 circRNAs showing significant expression changes. Intriguingly, 82 circRNAs are independently regulated to their host genes. We validated the same circRNA dynamics for circRNAs from ATXN10, CHD7, DNAJC6 and SLC8A1 in biopsy material from human dilated cardiomyopathy (DCM) and control patients. Finally, we could show that rodent homologs of circMYOD, circSLC8A1, circATXN7 and circPHF21A interact with either the ribosome or Argonaute2 protein complexes. Conclusion: CircRNAs are dynamically expressed in a hiPSC-CM model of cardiac development and stress response. Some circRNAs show similar, host-gene independent expression dynamics in patient samples and may interact with the ribosome and RISC complex. In summary, the hiPSC-CM model uncovered a new signature of potentially disease relevant circRNAs which may serve as novel therapeutic targets. (C) 2017 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Siede, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rapti, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gorska, A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Katus, H. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boeckel, J. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meder, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maack, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Voelkers, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, O. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Backs, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-222638
DOI:	10.1016/j.yjmcc.2017.06.015
Journal or Publication Title:	J. Mol. Cell. Cardiol.
Volume:	109
Page Range:	S. 48 - 57
Date:	2017
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1095-8584
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLURIPOTENT STEM-CELLS; CARDIOMYOCYTE DIFFERENTIATION; GENERATION; PROLIFERATION; HEARTS; MOUSE Multiple languages Cardiac & Cardiovascular Systems; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22263