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RNA Biol. 2017 Aug 3;14(8):1064-1074. doi: 10.1080/15476286.2016.1269999. Epub 2016 Dec 16.

Increased complexity of circRNA expression during species evolution.

Dong R1,2, Ma XK1,2, Chen LL3,2,4, Yang L1,2,4.

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a Key Laboratory of Computational Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences , Chinese Academy of Sciences , Shanghai , China.
c University of Chinese Academy of Sciences , Beijing , China.
b State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology , Chinese Academy of Sciences , Shanghai , China.
d School of Life Science and Technology, ShanghaiTech University , Shanghai , China.


Circular RNAs (circRNAs) are broadly identified from precursor mRNA (pre-mRNA) back-splicing across various species. Recent studies have suggested a cell-/tissue- specific manner of circRNA expression. However, the distinct expression pattern of circRNAs among species and its underlying mechanism still remain to be explored. Here, we systematically compared circRNA expression from human and mouse, and found that only a small portion of human circRNAs could be determined in parallel mouse samples. The conserved circRNA expression between human and mouse is correlated with the existence of orientation-opposite complementary sequences in introns that flank back-spliced exons in both species, but not the circRNA sequences themselves. Quantification of RNA pairing capacity of orientation-opposite complementary sequences across circRNA-flanking introns by Complementary Sequence Index (CSI) identifies that among all types of complementary sequences, SINEs, especially Alu elements in human, contribute the most for circRNA formation and that their diverse distribution across species leads to the increased complexity of circRNA expression during species evolution. Together, our integrated and comparative reference catalog of circRNAs in different species reveals a species-specific pattern of circRNA expression and suggests a previously under-appreciated impact of fast-evolved SINEs on the regulation of (circRNA) gene expression.


Alu; SINE; back-splicing; circRNA; complementary sequence; evolution; species-specific

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