title: The Biogenesis of Nascent Circular RNAs.
abstract: Steady-state circular RNAs (circRNAs) have been mapped to thousands of genomic loci in mammals. We studied circRNA processing using metabolic tagging of nascent RNAs with 4-thiouridine (4sU). Strikingly, the efficiency of circRNA processing from pre-mRNA is extremely low endogenously. Additional studies revealed that back-splicing outcomes correlate with fast RNA Polymerase II elongation rate and are tightly controlled by cis-elements in vivo. Additionally, prolonged 4sU labeling in cells shows that circRNAs are largely processed post-transcriptionally and that circRNAs are stable. Circular RNAs that are abundant at a steady-state level tend to accumulate. This is particularly true in cells, such as neurons, that have slow division rates. This study uncovers features of circRNA biogenesis by investigating the link between nascent circRNA processing and transcription.
authors.affiliation: State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, 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: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Siye
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China. Electronic address: liyang@picb.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China. Electronic address: linglingchen@sibcb.ac.cn.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D004004:Dichlororibofuranosylbenzimidazole / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology; D012313:RNA / Q000096:biosynthesis*; D012319:RNA Polymerase II / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D000079962:RNA, Circular; D017423:Sequence Analysis, RNA; D017381:Spliceosomes / Q000378:metabolism; D013891:Thiouridine / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000079962:RNA, Circular; D013891:Thiouridine; D004004:Dichlororibofuranosylbenzimidazole; D012313:RNA; D012319:RNA Polymerase II