Circular RNA Expression: Its Potential Regulation and Function

In 2012, a new feature of eukaryotic gene expression emerged: ubiquitous expression of circular RNA (circRNA) from genes traditionally thought to express messenger or linear noncoding (nc)RNA only. CircRNAs are covalently closed, circular RNA molecules that typically comprise exonic sequences and are spliced at canonical splice sites. This feature of gene expression was first recognized in humans and mouse, but it quickly emerged that it was common across essentially all eukaryotes studied by molecular biologists. CircRNA abundance, and even which alternatively spliced circRNA isoforms are expressed, varies by cell type and can exceed the abundance of the traditional linear mRNA or ncRNA transcript. CircRNAs are enriched in the brain and increase in abundance during fetal development. Together, these features raise fundamental questions regarding the regulation of circRNA in cis and in trans, and its function.

TrendsMany circRNAs have recently been discovered and characterized.Recently, much light has been shed on the regulation and function of circRNAsCircRNA has been posited to function as a miRNA or RNA-binding protein sponge. However, a general function has not been identified.Developmental regulation of circRNA and enrichment in the nervous system are an emerging theme shared by circRNAs across the metazoan lineage, from flies to humans.CircRNAs can be joined by 3′–5′ linkages, containing only exonic sequence; 2′–5′ linkages (intronic lariats); or 3′–5′ linkages that contain retained intronic sequences.