Protein-coding circular RNAs – mechanism, detection, and their role in cancer and neurodegenerative diseases

Abstract

Circular RNAs (circRNAs) are a unique class of non-coding RNAs and were originally thought to have no protein-coding potential due to their lack of a 5′ cap and 3′ poly(A) tail. However, recent studies have challenged this notion and revealed that some circRNAs have protein-coding potential. They have emerged as a key area of interest in cancer and neurodegeneration research as recent studies have identified several circRNAs that can produce functional proteins with important roles in cancer progression. The protein-coding potential of circRNAs is determined by the presence of an open reading frame (ORF) within the circular structure that can encode a protein. In some cases, the ORF can be translated into a functional protein despite the lack of traditional mRNA features. While the protein-coding potential of most circRNAs remains unclear, several studies have identified specific circRNAs that can produce functional proteins. Understanding the protein-coding potential of circRNAs is important for unravelling their biological functions and potential roles in disease. Our review provides comprehensive coverage of recent advances in the field of circRNA protein-coding capacity and its impact on cancer and neurodegenerative diseases pathogenesis and progression.