Circular RNAs: Characterization, cellular roles, and applications

• Published in: Cell 2022-06, Vol.185 (12), p.2016-2034
• Main Authors: Liu, Chu-Xiao, Chen, Ling-Ling
• Format: Article
• Language: English
• Subjects: aptamer; back-splicing; circRNA; circular RNA application; circular RNA modality; circular RNA therapeutics; circular RNA translation; immunogenicity; Proteins - metabolism; RBP; RNA - metabolism; RNA circle; RNA Precursors - metabolism; RNA Splicing; RNA, Circular; RNA, Messenger - metabolism; RNA-binding protein
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2022.04.021

Most circular RNAs are produced from the back-splicing of exons of precursor mRNAs. Recent technological advances have in part overcome problems with their circular conformation and sequence overlap with linear cognate mRNAs, allowing a better understanding of their cellular roles. Depending on their localization and specific interactions with DNA, RNA, and proteins, circular RNAs can modulate transcription and splicing, regulate stability and translation of cytoplasmic mRNAs, interfere with signaling pathways, and serve as templates for translation in different biological and pathophysiological contexts. Emerging applications of RNA circles to interfere with cellular processes, modulate immune responses, and direct translation into proteins shed new light on biomedical research. In this review, we discuss approaches used in circular RNA studies and the current understanding of their regulatory roles and potential applications. Circular RNAs are an exciting emerging class of RNA species, but their closed-loop structures and sequence similarity to linear RNAs have presented challenges in characterizing their unique roles. Liu and Chen review the growing toolbox to characterize circular RNA, the resulting emerging understanding of their biological roles, and how circular RNA are being utilized for biomedical applications.