Multifaceted roles of complementary sequences on circRNA formation

Abstract

Background: Circular RNAs (circRNAs) from back-spliced exon(s) are characterized by the covalently closed loop feature with neither 5′ to 3′ polarity nor polyadenylated tail. By using specific computational approaches that identify reads mapped to back-splice junctions with a reversed genomic orientation, ten thousands of circRNAs have been recently re-identified in various cell lines/tissues and across different species. Increasing lines of evidence suggest that back-splicing is catalyzed by the canonical spliceosomal machinery and modulated by cis-elements and trans-factors.

Results: In this mini-review, we discuss our current understanding of circRNA biogenesis regulation, mainly focusing on the complex regulation of complementary sequences, especially Alus in human, on circRNA formation.

Conclusions: Back-splicing can be significantly facilitated by RNA pair formed by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon(s). RNA pair formed within individual introns competes with RNA pair formed across flanking introns in the same gene locus, leading to distinct choices for either canonical splicing or back-splicing. Multiple RNA pairs that bracket different circle-forming exons compete for alternative back-splicing selection, resulting in multiple circRNAs generated in a single gene locus.

Graphical abstract

Keywords

circRNA / circRNA biogenesis / back-splicing / cis-elements / complementary sequences / Alu

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ACKNOWLEDGEMENTS

We are grateful to L.-L.C. for critical reading of this manuscript. We apologize to authors whose work could not be cited here owing to space/content limitations. Our work is supported by grants 2014CB910601 from MOST and 91540115 and 31471241 from NSFC.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Qin Yang, Ying Wang and Li Yang declare that they have no conflict of interests.

This article is a review article and does not contain any studies with human or animal subjects performed by any of the authors.

RIGHTS & PERMISSIONS

2017 Higher Education Press and Springer-Verlag Berlin Heidelberg