Abstract
Heart disease remains the leading cause of death globally and leads to tremendous socio-economic burden. Despite advances in the field of cardiovascular research, novel theranostics are still in urgent need. Remarkable progress has been made in understanding aberrant protein interactions and signaling pathways in the diseased heart, but less is known regarding epigenetic regulation. Non-coding RNAs have emerged as important regulators of cardiac function and have been implicated in disease. While significant progress has been made in understanding the roles of microRNAs and long non-coding RNAs, the functional roles of circular RNAs are less explored. Recent studies have provided ample evidence supporting their roles in multiple physiological processes including regulating the function of the heart. Compared with other RNAs, circular RNAs exhibit higher stability and more versatile functional modes: including sponging microRNAs, scaffolding proteins, regulating transcription, and even encoding small regulatory peptides. These characteristics make circular RNAs promising candidates for the development of diagnostic tools and therapies for heart disease. In this review, we will discuss the biogenesis of circular RNAs and provide an update of their functional implications in heart disease, with an emphasis on heart failure and arrhythmias.
Highlights
Most RNAs exist in the linear form as a direct result of the transcription
Circular RNAs generated from precursor mRNAs through backsplicing or from splicing lariats that escaped from debranching have become a new research front across disciplines [4,5,6,7]
With growing evidence of non-coding RNA participating in heart disease progression, they have emerged as promising targets for diagnosis and treatment
Summary
Most RNAs exist in the linear form as a direct result of the transcription. post-transcriptional processing leads to the generation of various groups of circular RNAs. RNAs to refer to circRNAs and ciRNAs. RNAs to refer to circRNAs and ciRNAs Most of such circular RNAs express at low levels and are not conserved during evolution [4,5], resembling less conserved microRNAs [8,9,10]. Heart disease remains the leading cause of death worldwide, the development of novel theranostics is still required. With growing evidence of non-coding RNA participating in heart disease progression, they have emerged as promising targets for diagnosis and treatment. Substantial progress has been made in understanding the functional roles of microRNAs and long non-coding RNAs in heart disease, far less is known about the roles of circular RNAs. In this review, we will introduce known mechanisms of circular RNAs biogenesis and functional modes in general, as well as their implications in heart failure and arrhythmias
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