A landscape of circular RNA expression in the human heart

Tan, Wilson Lek Wen; Lim, Boon Whatt; Anene-Nzelu, Chukwuemeka George; Ackers‐Johnson, Matthew; Dashi, Albert; See, Kelvin; Tiang, Zenia; Lee, Dominic Paul; Chua, Wee Woon; Luu, Tuan Danh Anh; Li, Peter Y. Q.; Richards, A. Mark; Foo, Roger

doi:10.1093/cvr/cvw250

Cited by 193 publications

(266 citation statements)

References 53 publications

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“…This is supported by evidence from Boeckel et al who have shown that the circRNA, cZNF292, is regulated by hypoxia in endothelial cells and controls angiogenesis. circRNAs are highly expressed in human heart tissue and are associated with key cardiac genes including Titin (TTN), RYR2 , and DMD (Tan et al, 2017). Further evidence for the role of circRNA in cardiovascular disease is supported by research from Jakobi et al who performed RNA-seq on adult murine hearts and identified a further 575 candidate cardiac circRNAs (Jakobi et al, 2016).…”

Section: Circrnas and Human Diseasementioning

confidence: 99%

Circular RNAs: Biogenesis, Function and Role in Human Diseases

Greene

Baird

Brady

et al. 2017

Front. Mol. Biosci.

477

385

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Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3′ and 5′ ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization. Interestingly, they have been found to be abundant, evolutionally conserved and relatively stable in the cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription. It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression. circRNAs appear to be more often downregulated in tumor tissue compared to normal tissue and this may be due to (i) errors in the back-splice machinery in malignant tissues, (ii) degradation of circRNAs by deregulated miRNAs in tumor tissue, or (iii) increasing cell proliferation leading to a reduction of circRNAs. circRNAs have been identified in exosomes and more recently, chromosomal translocations in cancer have been shown to generate aberrant fusion-circRNAs associated with resistance to drug treatments. In addition, though originally thought to be non-coding, there is now increasing evidence to suggest that select circRNAs can be translated into functional proteins. Although much remains to be elucidated about circRNA biology and mechanisms of gene regulation, these ncRNAs are quickly emerging as potential disease biomarkers and therapeutic targets in cancer.

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Section: Circrnas and Human Diseasementioning

confidence: 99%

Circular RNAs: Biogenesis, Function and Role in Human Diseases

Greene

Baird

Brady

et al. 2017

Front. Mol. Biosci.

477

385

View full text Add to dashboard Cite

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“…Due to the advanced sequencing technology and data analysis methods, a growing number of circRNAs have been uncovered from human and murine hearts [84,85,86]. The first circRNA profiling study has identified 575 circRNA species from adult murine hearts and showed that several circRNAs are relevant for the cardiovascular disease pathogenesis [85].…”

Section: Circrnas and Cardiac Remodelingmentioning

confidence: 99%

“…The comparative analyses of the circRNA expression from rats (neonatal and adult), mice (sham or after TAC) and humans (failing, non-failing) have detected more than 9000 candidate circRNAs from each species [86]. Recently, a detailed annotation and analysis of genome-wide circRNA expression uncovered 15,318 cardiac circRNAs in the human heart [84]. All of these provide a good basis for studying the role of circRNAs in heart disease.…”

Section: Circrnas and Cardiac Remodelingmentioning

confidence: 99%

The Role and Molecular Mechanism of Non-Coding RNAs in Pathological Cardiac Remodeling

Gao

Wang

et al. 2017

IJMS

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Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins. Studies show that ncRNAs are not only involved in cell proliferation, apoptosis, differentiation, metabolism and other physiological processes, but also involved in the pathogenesis of diseases. Cardiac remodeling is the main pathological basis of a variety of cardiovascular diseases. Many studies have shown that the occurrence and development of cardiac remodeling are closely related with the regulation of ncRNAs. Recent research of ncRNAs in heart disease has achieved rapid development. Thus, we summarize here the latest research progress and mainly the molecular mechanism of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in cardiac remodeling, aiming to look for new targets for heart disease treatment.

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“…11 This study identifies thousands of potential circRNAs that might be involved in cardiomyocyte biology and increases our knowledge on the potential role of this type of ncRNAs in the heart, which has been limited so far to one manuscript from Engelhardt's group. 12 Specifically, the authors analysed ribominus RNAs from human and mouse failing and non-failing hearts, including also data from human embryonic stem cell-derived cardiomyocytes at different stages of differentiation.…”

mentioning

confidence: 99%

Circular RNAs and heart failure: new players for an old disease

Elia

Quintavalle

Condorelli

2017

Cardiovascular Research

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This editorial refers to 'A landscape of circular RNA expression in the human heart' by W.L.W. Tan et al., pp. 298-309.The heart is the central organ of the circulatory system, and its contractile activity is mainly due to cardiomyocytes. Transcriptomic analysis of cellular contents has revealed that only 2% of total RNA is translated into proteins, indicating the existence of a huge amount of non-coding RNAs (ncRNAs). Among these transcripts, many different regulatory RNAs have been identified, divided into two main classes: short and long ncRNAs. While several studies have highlighted the role of microRNAs -short ncRNAs of around 22bp in length -in the regulation of cardiomyocyte biology during development and adulthood, there is still a huge lack of information on the role of long ncRNAs in this regard. Recently, highthroughput sequencing and novel computational approaches have demonstrated that the long ncRNA species named circular RNAs (circRNAs)-previously considered of low abundance and likely deriving from errors in splicing 1 -has indeed a fundamental role in the regulation of gene expression 2,3 but might also work as potential circulating biomarkers for human pathologies. 4 CircRNAs derive from an alternative splicing of linear transcripts, showing covalent closed loop structures with neither 5'-3' polarity nor a polyadenylated tail and with exonic or intronic origins. 5 This specific structure allows them to be more stable in vivo than their linear counterparts. In terms of cellular localization, exonic circRNAs are predominantly located in the cytoplasm, 3 while intronic are mainly nuclear. 2How circRNAs are generated in mammals is still not clear, but two putative mechanisms have been proposed: direct back-splicing and exon skipping.6 Direct back-splicing involves the pairing of an upstream donor and a downstream splice acceptor sequence, that results in the circularization of the specific RNA. On the other hand, exon skipping might involve the formation of a lariat that promotes circularization. Both mechanisms involve the canonical spliceosome apparatus. 7 Moreover, recent studies have also shown that circularization is facilitated by complementary sequences, such as Arthrobacter luteus (ALU) sequences 8,9 and involves the activity of specific protein factors, such as the alternative splicing factor Quaking (QKI). 10In terms of biological activity, they might play different roles: intronic circRNAs have been found to regulate Polymerase II recruitment on specific genes; 2 exonic ciRNAs have been shown to act as miRNA sponges to regulate gene expression. 3 However, our knowledge about circRNAs in the human heart is still limited, thereby new studies on their role in cardiac pathogenesis might reveal novel pathways, possibly leading to the identification of new therapeutic strategies for life-threatening heart diseases. Tan and colleagues provide in the current issue of Cardiovascular Research detailed genome-wide landscape maps of circRNA expression in humans and mouse cardiac tissue.11 This study...

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A landscape of circular RNA expression in the human heart

Abstract: Our data provide a detailed circRNA expression landscape in hearts. There is a high-abundance of specific cardiac-expressed circRNA. These findings open up a new avenue for future investigation into this emerging class of RNA.

Cited by 193 publications

References 53 publications

Circular RNAs: Biogenesis, Function and Role in Human Diseases

Circular RNAs: Biogenesis, Function and Role in Human Diseases

The Role and Molecular Mechanism of Non-Coding RNAs in Pathological Cardiac Remodeling

Circular RNAs and heart failure: new players for an old disease

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