Following improvement and integration of novel genome sequencing techniques, a new stage light has been shone upon circular RNAs (circRNA) in regard to their structure and functionality. In comparison to their linear counterparts, circRNA possess a multitude of remarkable functions such as microRNA (miRNA) sponging, RNA-binding protein (RBP) regulation and translational capabilities whose research have recently gained traction. Comprehensive computational modelling and analysis have revealed the relationship between the sequence composition of circRNAs and their biogenesis and structural formation as well as spatial identification. Due to fluctuations in expressional activity in tissue-specific environments and stimulations by tumour cells, circRNAs have sparked considerable interest in being employed as plausible biomarkers in disease control and treatment as consequence of their impressive specificity and biocompatibility. Additionally, an increasing number of studies have proposed them as viable solutions to be just as competent as presently used disease markers and medicine, if not better.
Researchers from University College London briefly summarize the characteristics, biogenesis and function of circRNA and introduced the potential applications and prospects of circRNA. With vigorous research being carried out regarding their still unclear diversified roles and precise molecular structure, circRNAs are bound to become the new revolutionary perspective on cellular regulation, protein signalling and disease pathogenesis.
Overview of the Biogenesis and Functionality of Circular RNA. Explanation and Footnotes
a A messenger RNA in its mature form, in which interaction between both the exons and introns are absent. b Lariat-Driven Circularisation. The upstream exon (exon 1) and downstream exon (exon 4) are covalently bonded due to the mRNA being spliced. This facilitates the production of a RNA lariat alongside paired-up exons that remain, which are Exons 2 and 3. c RNA-Binding Protein Driven and Intron-pairing Driven Circularisations. In both cases, the upstream and downstream introns (introns 1 and 3) are paired up to provide opportunity for the sandwiched Exons (exons 2 and 3) to interact, the only difference is that with the former case, an external RBP molecule joins the equation to actively facilitate the reaction, whereas with Intron-pairing Driven Circularisation, the hydroxyl group and the phosphate group of the upstream and downstream introns respectively pair up independently. d ecircRNA or ElcircRNA is produced regardless of Circularisation route. In some cases, intronic segments resides in the loop, hence giving rise to ElcircRNAs as opposed to ecircRNA which contains purely exonic segments. e Functionalities of mature circRNAs include miRNA sponging, acting as a double inhibitor for some chemical reactions; Protein Translation is possible, albeit quite rare and research is being carried to understand how it differs from linear RNA translations; RBP-Protein Complex formations help regulate and moderate pathways and indirectly impact the production of other circRNAs; mRNA Interactions, be it facilitative or inhibitory