Circular RNAs: splicing’s enigma variations

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Abstract
Circular (circ)RNAs are to transcriptomics what the famous hidden musical theme is to Elgar's Enigma Variations : woven into the entire composition but not unambiguously identified or understood by scholars to this day. Now, two studies (Hansen et al , 2013; Memczak et al , 2013) have made substantial progress in both, identifying thousands of circRNAs and beginning to crack the enigma of their cellular function, by demonstrating that the circRNAs CiRS‐7/CDR1as and SRY function as natural and highly stable sponges for specific microRNAs. Much work over decades has documented the complex ways in which genetic information is transcribed and processed into functional RNAs to ultimately shape phenotypes. Well‐appreciated phenomena include alternative promoter choice, splicing, editing and 3′ end formation to generate surprisingly diverse mRNA populations, as well as the widespread, regulated and complex production of non‐coding RNAs from genic as well as intergenic regions of the genome, reviewed in Mercer et al (2012). Occasional evidence for the formation of circular RNAs (circRNAs) had also been presented over the years and examples such as the circular testis‐determining RNA SRY have achieved some prominence (Capel et al , 1993). Nevertheless, circRNAs have mostly been disregarded as rare, some form of transcriptional noise or RT–PCR artefacts. Thus, demonstrations of their widespread and substantial presence within transcriptomes have only recently come to the fore (Salzman et …