Abstract
Circular RNAs (circRNAs) are classified as long non-coding RNAs (lncRNAs) that are characterized by a covalent closed-loop structure. This closed-loop shape is the result of a backsplicing event in which the 3' and 5' splice sites are ligated. Through the lack of 3' poly(A) tails and 5' cap structures, circRNAs are more stable than linear RNAs because these adjustments make the circular loop less susceptible to exonucleases. The majority of identified circRNAs possess cell‐ and tissue-specific expression patterns. In addition, high-throughput RNA-sequencing combined with novel bioinformatics algorithms revealed that circRNA sequences are often conserved across different species suggesting a positive evolutionary pressure. Implicated as regulators of protein turnover, micro RNA (miRNA) sponges, or broad effectors in cell differentiation, proliferation, and senescence, research of circRNA has increased in recent years. Particularly in cardiovascular research, circRNA-related discoveries have opened the door for the development of potential diagnostic and therapeutic tools. Increasing evidence links deviating circRNA expression patterns to various cardiovascular diseases including ischemic heart failure. In this mini-review, we summarize the current state of knowledge on circRNAs in cardiac regeneration with a focus on cardiac cell proliferation, differentiation, cardiomyocyte survival, and cardiac reprogramming.
Highlights
98% of the human genome is comprised of non-coding RNA transcripts (Bär et al, 2020)
The circular variant was found to be more highly transcribed than the linear version (Salzman et al, 2012; Lasda and Parker, 2016). In this mini-review, we provide a short overview on circRNA biogenesis and their mechanism of action in general
A total of 226 differentially regulated circRNAs were discovered regarding differentiation of umbilical cord-derived human mesenchymal stem cells (MSCs) into cardiomyocytes, with the most highly differentially regulated circRNAs related to differentiation and proliferation pathways, including the Wnt pathway (Ruan et al, 2019)
Summary
98% of the human genome is comprised of non-coding RNA (ncRNA) transcripts (Bär et al, 2020). Protein-coding genes remain the most well-studied sequences in the mammalian genome (Esteller, 2011). It became apparent that ncRNAs are crucially involved in a wide array of physiological and pathophysiological processes (Brennecke et al, 2003; Xu et al, 2003; Abbaszadeh-Goudarzi et al, 2020; Hashemian et al, 2020; Yousefi et al, 2020). One recently re-discovered class of ncRNAs is circRNAs
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