Abstract
Circular RNAs (circRNAs) are a distinctive class of regulatory non-coding RNAs characterised by the presence of covalently closed ends. They are evolutionary conserved molecules, and although detected in different tissues, circRNAs resulted specifically enriched in the nervous system. Recent studies have shown that circRNAs are dynamically modulated during neuronal development and aging, that circRNAs are enriched at synaptic levels and resulted modulated after synaptic plasticity induction. This has suggested that circRNAs might play an important role in neuronal specification and activity. Despite the exact function of circRNAs is still poorly understood, emerging evidence indicates that circRNAs have important regulatory functions that might extensively contribute to the dynamic modulation of gene expression that supports neuronal pathways. More interestingly, deregulation of circRNAs expression has been linked with various pathological conditions. In this review, we describe current advances in the field of circRNA biogenesis and function in the nervous system both in physiological and in pathological conditions, and we specifically lay out their association with neurodegenerative diseases. Furthermore, we discuss the opportunity to exploit circRNAs for innovative therapeutic approaches and, due to their high stability, to use circRNAs as suitable biomarkers for diagnosis and disease progression.
Highlights
In the last decade, fast advances in the resolution of high-throughput technologies dramatically improved our understanding of transcriptome diversity of complex organisms [1]
Even though not much is known about circRNA mode of action, the few species characterized have been shown to act as molecular decoy for microRNAs or RNA binding proteins (RBPs) [3,5,6,7,8,9,10,11], to control transcription of their host genes [12,13,14] and, classify as non-coding RNAs (ncRNAs), some of them hold the capacity to direct synthesis of short peptides/proteins [15,16,17,18,19,20]
In this review describes the current knowledge of circRNA biogenesis and function, the evidence supporting their specific activity in the nervous system and their putative implication in neurological disorders
Summary
Fast advances in the resolution of high-throughput technologies dramatically improved our understanding of transcriptome diversity of complex organisms [1]. Even though not much is known about circRNA mode of action, the few species characterized have been shown to act as molecular decoy for microRNAs (miRNAs) or RNA binding proteins (RBPs) [3,5,6,7,8,9,10,11], to control transcription of their host genes [12,13,14] and, classify as ncRNAs, some of them hold the capacity to direct synthesis of short peptides/proteins [15,16,17,18,19,20] This strongly supports the hypothesis that neuronal cells might rely on the activity of these transcripts to precisely regulate gene expression in time and space.
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