Molecular basis of backsplicing regulation and its application to manipulate circRNA levels

Abstract

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which have been implicated in both physiology and human diseases. Most circRNAs are typically generated through backsplicing, where a downstream splice donor is covalently joined to an upstream splice acceptor. Backsplicing is dependent on the spliceosome machinery and is precisely controlled by various cis-elements and trans-factors. In the present review, we summarize the molecular mechanisms of backsplicing regulation as well as their physiological and pathological significance. Additionally, we discuss the strategies to manipulate circRNA expression in vivo and in vitro, aiming to explore the application of circRNA biogenesis in the diagnosis and therapy of human diseases.