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Quantitative Biology

Quant. Biol.    2017, Vol. 5 Issue (3) : 205-209     DOI: 10.1007/s40484-017-0112-7
Multifaceted roles of complementary sequences on circRNA formation
Qin Yang1, Ying Wang1, Li Yang1,2()
1. CAS Key Laboratory of Computational Biology, Collaborative Innovation Center of Genetics and Development, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai 200031, China
2. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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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.

Author Summary  A large amount of circRNAs have been recently re-discovered from thousands of gene loci in various cell lines/tissues and across different species, and have been suggested to play important roles in gene expression regulation with different mechanisms of action. These results thus expand our understanding on the complexity and diversity of eukaryotic circular RNAs. Recent studies have shown that both cis-elements and trans-factors can promote back-splicing for circRNA biogenesis. We review recent research progress on the regulation of circRNA biogenesis, focusing on our current understanding of the complex regulation of cis complementary sequences, especially Alus in human, on circRNA formation.
Keywords circRNA      circRNA biogenesis      back-splicing      cis-elements      complementary sequences      Alu     
Corresponding Authors: Li Yang   
Just Accepted Date: 21 June 2017   Online First Date: 28 July 2017    Issue Date: 24 August 2017
 Cite this article:   
Qin Yang,Ying Wang,Li Yang. Multifaceted roles of complementary sequences on circRNA formation[J]. Quant. Biol., 2017, 5(3): 205-209.
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Fig.1  Schematic models of multifaceted roles of complementary sequences on circRNA formation.
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