Biogenesis and Regulatory Roles of Circular RNAs

Covalently closed, single-stranded circular RNAs can be produced from viral RNA genomes as well as from the processing of cellular housekeeping noncoding RNAs and precursor messenger RNAs. Recent transcriptomic studies have surprisingly uncovered that many protein-coding genes can be subjected to backsplicing, leading to widespread expression of a specific type of circular RNAs (circRNAs) in eukaryotic cells. Here, we discuss experimental strategies used to discover and characterize diverse circRNAs at both the genome and individual gene scales. We further highlight the current understanding of how circRNAs are generated and how the mature transcripts function. Some circRNAs act as noncoding RNAs to impact gene regulation by serving as decoys or competitors for microRNAs and proteins. Others form extensive networks of ribonucleoprotein complexes or encode functional peptides that are translated in response to certain cellular stresses. Overall, circRNAs have emerged as an important class of RNA molecules in gene expression regulation that impact many physiological processes, including early development, immune responses, neurogenesis, and tumorigenesis.

Automated summary

Covalently closed, single-stranded circular RNAs can be produced from viral RNA genomes as well as from the processing of cellular RNAs. Recent studies have revealed that many protein-coding genes can undergo backsplicing, leading to widespread expression of circular RNAs (circRNAs) in eukaryotic cells. circRNAs play various roles in gene regulation, acting as noncoding RNAs or encoding functional peptides. They are involved in physiological processes including early development, immune responses, neurogenesis, and tumorigenesis.