title: Metazoan tRNA introns generate stable circular RNAs in vivo.
abstract: We report the discovery of a class of abundant circular noncoding RNAs that are produced during metazoan tRNA splicing. These transcripts, termed tRNA intronic circular (tric)RNAs, are conserved features of animal transcriptomes. Biogenesis of tricRNAs requires anciently conserved tRNA sequence motifs and processing enzymes, and their expression is regulated in an age-dependent and tissue-specific manner. Furthermore, we exploited this biogenesis pathway to develop an in vivo expression system for generating "designer" circular RNAs in human cells. Reporter constructs expressing RNA aptamers such as Spinach and Broccoli can be used to follow the transcription and subcellular localization of tricRNAs in living cells. Owing to the superior stability of circular vs. linear RNA isoforms, this expression system has a wide range of potential applications, from basic research to pharmaceutical science.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Grigory S
authors.initials: GS
authors.lastname: Filonov
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Noto
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Schmidt
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Talia L
authors.initials: TL
authors.lastname: Hatkevich
authors.affiliation: Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Samie R
authors.initials: SR
authors.lastname: Jaffrey
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: A Gregory
authors.initials: AG
authors.lastname: Matera
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics*; D005260:Female; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D007438:Introns; D008297:Male; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D020871:RNA Stability; D000079962:RNA, Circular; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics*; D059467:Transcriptome
chemical_list: D000079962:RNA, Circular; D012313:RNA; D012343:RNA, Transfer
keywords: circular RNA; expression system; noncoding RNA, ncRNA; tRNA processing