Molecular mechanisms of circular RNA translation

Circular RNAs (circRNAs) are covalently closed single-stranded RNAs without a 5′ cap structure and a 3′ poly(A) tail typically present in linear mRNAs of eukaryotic cells. CircRNAs are predominantly generated through a back-splicing process within the nucleus. CircRNAs have long been considered non-coding RNAs seemingly devoid of protein-coding potential. However, many recent studies have challenged this idea and have provided substantial evidence that a subset of circRNAs can associate with polysomes and indeed be translated. Therefore, in this review, we primarily highlight the 5’ cap-independent internal initiation of translation that occurs on circular RNAs. Several molecular features of circRNAs, including the internal ribosome entry site, N6-methyladenosine modification, and the exon junction complex deposited around the back-splicing junction after back-splicing event, play pivotal roles in their efficient internal translation. We also propose a possible relationship between the translatability of circRNAs and their stability, with a focus on nonsense-mediated mRNA decay and nonstop decay, both of which are well-characterized mRNA surveillance mechanisms. An in-depth understanding of circRNA translation will reshape and expand our current knowledge of proteomics. This research delves into the intricate realm of circular RNAs (circRNAs), a kind of RNA molecule that forms a covalently closed circular structure, making it more stable than its linear counterparts. Despite being plentiful in cells, the role of circRNAs is largely a mystery. The researchers provide a summary of the various ways circRNAs are created and outline the different functions they can have. They also explore the molecular specifics of how circRNAs are translated and consider the potential interaction between this translation and their stability. The research is a review, summarizing and analyzing existing studies on the subject and highlighting the role and potential impact of circRNAs in the regulation of gene expression. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.