Circular RNA Expression: Its Potential Regulation and Function

Abstract

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.

Keywords: RNA; RNA splicing; circRNA; circular RNA.

Figure 1. The sequence of circular RNA comprises exons from protein and noncoding loci, spliced at canonical splice sites

Bi-colored reads represent paired-end RNA-Seq reads used to discover circular RNA that are enriched in polyA-depleted RNA samples.