Biological functions and applications of circRNAs—next generation of RNA-based therapy

Abstract

Circular RNAs (circRNAs) are unique single-stranded RNA molecules that are covalently closed and expressed in a tissue- and cell-specific manner. Most circRNAs are formed by back-splicing of pre-mRNA and have a wide range of functions in cells. As they lack a 5'-cap and a 3'-poly(A) tail, they are classified as noncoding RNAs that act as sponges for miRNAs and RNA-binding proteins. However, recent studies have found that some circRNAs can undergo cap-independent translation, making them capable of encoding proteins through alternative translation initiation mechanisms. CircRNAs are more stable than linear mRNAs due to their unique circular structure. With mRNA-based drugs receiving significant attention in the past two years, mRNA's instability and immunogenicity are major obstacles to its widespread use. Since circRNA is more stable than mRNA and less immunogenic and can be translated in a tissue-specific manner, it is a promising modality for RNA therapy. In this review, we will provide an overview of the biological functions and potential applications of circRNA.