Protein coding circular RNAs in Human Diseases

Abstract

Circular RNAs (circRNAs) are a unique class of closed-loop RNA molecules formed through back-splicing of precursor mRNAs that exhibit diverse biological functions. Recent evidence highlights their emerging roles as protein-coding entities, particularly in cancer biology. This review explores the cap-independent translation mechanisms of circRNAs, focusing on internal ribosome entry sites and N6-methyladenosine modifications. We further summarize the biological roles of circRNA-encoded proteins and their relevance to human diseases. Additionally, the review addresses key challenges in circRNA research and provides perspectives on their promising potential in disease diagnosis and therapeutic applications.