Circular exonic RNAs: When RNA structure meets topology

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    Although RNA circularization was first documented in the 1990s, the extent to which it occurs was not known until recent advances in high-throughput sequencing enabled the widespread identification of circular RNAs (circRNAs). Despite this, many aspects of circRNA biogenesis, structure, and function yet remain obscure. This review focuses on circular exonic RNAs, a subclass of circRNAs that are generated through backsplicing. Here, I hypothesize that RNA secondary structure can be the common factor that promotes both exon skipping and spliceosomal RNA circularization, and that backsplicing of double-stranded regions could generate topologically linked circRNA molecules. CircRNAs manifest themselves by the presence of tail-to-head exon junctions, which were previously attributed to post-transcriptional exon permutation and repetition. I revisit these observations and argue that backsplicing does not automatically imply RNA circularization because tail-to-head exon junctions give only local information about transcript architecture and, therefore, they are in principle insufficient to determine globally circular topology. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.

    Original languageEnglish
    Article number194384
    JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
    Issue number11-12
    Publication statusPublished - 1 Nov 2019


    • Backsplicing
    • CircRNA
    • Circular exonic RNAs
    • Non-collinear
    • Post-transcriptional exon shuffling
    • RNA structure
    • Topology
    • Trans-splicing


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