title: Complementary sequence-mediated exon circularization.
abstract: Exon circularization has been identified from many loci in mammals, but the detailed mechanism of its biogenesis has remained elusive. By using genome-wide approaches and circular RNA recapitulation, we demonstrate that exon circularization is dependent on flanking intronic complementary sequences. Such sequences and their distribution exhibit rapid evolutionary changes, showing that exon circularization is evolutionarily dynamic. Strikingly, exon circularization efficiency can be regulated by competition between RNA pairing across flanking introns or within individual introns. Importantly, alternative formation of inverted repeated Alu pairs and the competition between them can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene. Collectively, exon circularization mediated by complementary sequences in human introns and the potential to generate alternative circularization products extend the complexity of mammalian posttranscriptional regulation.
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: linglingchen@sibcb.ac.cn.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: liyang@picb.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D017398:Alternative Splicing; D020087:Alu Elements; D000818:Animals; D001483:Base Sequence; D053595:Embryonic Stem Cells / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons; D015894:Genome, Human; D006801:Humans; D007438:Introns; D008322:Mammals / Q000235:genetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016415:Sequence Alignment