Abstract
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.
Highlights
There has been a growing interest in circular RNAs since they are involved in a wide spectrum of cellular functions that might have a large impact on phenotype and disease
Circular RNA were rediscovered a few years ago as non-canonically spliced RNA forms present in different organisms including humans (Salzman et al, 2012; Jeck et al, 2013). They are covalently closed transcripts formed through an RNA back-splicing event, where a splice donor of a downstream exon joins to an upstream splice acceptor leading to covalently closed transcripts that are characterized by the presence of a back-splicing junction that makes circRNAs distinguishable from their linear counterparts (Figure 1A) (Zhang et al, 2016; Wilusz, 2018)
The circRNA field is still at an early stage, circRNAs have already shown to be astonishing molecules, implicated in many processes, with a great biomarker potential and that can change the way we understand the transcription and translation processes. They are gaining attention and the circRNA field is at the moment one of the most active RNA research fields
Summary
CircRNAs are no longer the only transcripts containing such a junction since recent studies have revealed that circular DNAs are common and can be transcribed resulting in transcripts that would mimic a circRNA signal. This new type of chimeric transcript can change the way in which circRNA analysis is being done and impact some of the results already reported
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