Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/118323
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Type: Journal article
Title: Insights into the biogenesis and potential functions of exonic circular RNA
Author: Ragan, C.
Goodall, G.J.
Shirokikh, N.E.
Preiss, T.
Citation: Scientific Reports, 2019; 9(1):2048-1-2048-18
Publisher: Springer Nature
Issue Date: 2019
ISSN: 2045-2322
2045-2322
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Responsibility: 
Chikako Ragan, Gregory J. Goodall, Nikolay E. Shirokikh, Thomas Preiss
Abstract: Circular RNAs (circRNAs) exhibit unique properties due to their covalently closed nature. Models of circRNAs synthesis and function are emerging but much remains undefined about this surprisingly prevalent class of RNA. Here, we identified exonic circRNAs from human and mouse RNA-sequencing datasets, documenting multiple new examples. Addressing function, we found that many circRNAs co-sediment with ribosomes, indicative of their translation potential. By contrast, circRNAs with potential to act as microRNA sponges were scarce, with some support for a collective sponge function by groups of circRNAs. Addressing circRNA biogenesis, we delineated several features commonly associated with circRNA occurrence. CircRNA-producing genes tend to be longer and to contain more exons than average. Back-splice acceptor exons are strongly enriched at ordinal position 2 within genes, and circRNAs typically have a short exon span with two exons being the most prevalent. The flanking introns either side of circRNA loci are exceptionally long. Of note also, single-exon circRNAs derive from unusually long exons while multi-exon circRNAs are mostly generated from exons of regular length. These findings independently validate and extend similar observations made in a number of prior studies. Furthermore, we analysed high-resolution RNA polymerase II occupancy data from two separate human cell lines to reveal distinctive transcription dynamics at circRNA-producing genes. Specifically, RNA polymerase II traverses the introns of these genes at above average speed concomitant with an accentuated slow-down at exons. Collectively, these features indicate how a perturbed balance between transcription and linear splicing creates important preconditions for circRNA production. We speculate that these preconditions need to be in place so that looping interactions between flanking introns can promote back-splicing to raise circRNA production to appreciable levels.
Keywords: Animals; Humans; Mice; MicroRNAs; RNA; RNA Splicing; Alternative Splicing; Base Sequence; Introns; Exons; Databases, Genetic; RNA, Circular
Rights: © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030110540
DOI: 10.1038/s41598-018-37037-0
Grant ID: http://purl.org/au-research/grants/nhmrc/1126711
http://purl.org/au-research/grants/arc/DP180100111
Appears in Collections:Medicine publications

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