To Be or Not to Be: Circular RNAs or mRNAs From Circular DNAs?

In recent years, there has been a growing interest in circular RNAs (circRNAs) since they are involved in a wide spectrum of cellular functions that might have a large impact on phenotype and disease. CircRNAs are mainly recorded by RNA-Seq and computational methods focused on the detection of back-splicing junction sequences considered the diagnostic feature of circRNAs. While some protocols remove linear RNA prior to sequencing, many have characterized circRNAs by sorting through total RNA sequencing data without excluding the possibility that some linear RNA can provide the same signal as a circRNA. Recent studies have revealed that circular DNAs of chromosomal origin are common in eukaryotic genomes and that they can be transcribed. Transcription events across the junction of circular DNAs would result in a transcript with a junction similar to those present in circRNAs. Therefore, in this report, we want to draw attention to transcripts from such circular DNAs both as an interesting new player in the transcriptome and also as a confounding factor that must be taken into account when studying circRNAs.