The circular RNA landscape: Biogenesis, functions, identification pipelines, and biomedical applications

Circular RNAs (circRNAs), a subtype of RNA molecules, possess distinctive characteristics, including their closed circular structure, stability, tissue specificity and long half-life compared to their linear counterparts. Initially presumed to be non-functional byproducts of splicing, advances in RNA-seq and bioinformatics have revealed the existence of these RNAs and begun to clarify their functions. Insight into their diverse functions revealed their roles, including regulating various cellular processes such as gene expression, transcription, translation into proteins (e.g., cap-independent translation), binding to microRNAs (miRNAs), and interacting with proteins. Moreover, mitochondria-encoded circular RNAs (mecciRNAs) have emerged as a novel subclass of circRNAs. Notably circRNAs have been associated with the development or progression of diseases (e.g., cancer, cardiometabolic and neurodegenerative disorders), highlighting diagnostic and therapeutic potential. In our review, we aim to summarize the current knowledge on circRNAs, covering their biogenesis, functions, identification tools, and potential biomedical applications.