Squaring the RNA circle

Two European teams have provided the strongest evidence to date that circular RNAs are widely expressed in human cells and have clear regulatory functions.1,2 The biomedical relevance of circular RNAs remains largely unexplored, but the recent explosion of studies linking noncoding RNAs to disease may portend a similar trajectory for this emerging class of nucleic acids.

The refinement of high throughput sequencing methods over the past decade has led to the discovery of thousands of noncoding RNAs, including numerous microRNAs and long noncoding RNAs. Although initial studies were primarily catalogs of RNA transcripts,3 subsequent functional analyses demonstrated that these molecules have widespread regulatory roles in human diseases.4

Numerous companies are now developing therapeutics or diagnostics that use or target miRNAs or lncRNAs in indications ranging from cardiovascular disease to cancer.

Although a handful of studies had suggested some individual RNA transcripts might exist in a circular form, until last year there were no reports of widespread RNA circles. That changed in 2012, when separate groups from Stanford University and The University of North Carolina at Chapel Hill School of Medicine published analyses of RNA sequencing data from human cells, suggesting thousands of transcripts may exist in a circular

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