title: Circular RNA is expressed across the eukaryotic tree of life.
abstract: An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons. Here we report that circular RNA isoforms are found in diverse species whose most recent common ancestor existed more than one billion years ago: fungi (Schizosaccharomyces pombe and Saccharomyces cerevisiae), a plant (Arabidopsis thaliana), and protists (Plasmodium falciparum and Dictyostelium discoideum). For all species studied to date, including those in this report, only a small fraction of the theoretically possible circular RNA isoforms from a given gene are actually observed. Unlike metazoans, Arabidopsis, D. discoideum, P. falciparum, S. cerevisiae, and S. pombe have very short introns (∼ 100 nucleotides or shorter), yet they still produce circular RNAs. A minority of genes in S. pombe and P. falciparum have documented examples of canonical alternative splicing, making it unlikely that all circular RNAs are by-products of alternative splicing or 'piggyback' on signals used in alternative RNA processing. In S. pombe, the relative abundance of circular to linear transcript isoforms changed in a gene-specific pattern during nitrogen starvation. Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Wang
authors.affiliation: Department of Plant Biology, Carnegie Institution for Science, Stanford, California, United States of America; Temasek Lifesciences Laboratory, National University of Singapore, Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Plant Biology, Carnegie Institution for Science, Stanford, California, United States of America; Temasek Lifesciences Laboratory, National University of Singapore, Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
authors.forename: Muh-Ching
authors.initials: MC
authors.lastname: Yee
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Barrett
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hogan
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Mari N
authors.initials: MN
authors.lastname: Olsen
authors.affiliation: Department of Plant Biology, Carnegie Institution for Science, Stanford, California, United States of America; Temasek Lifesciences Laboratory, National University of Singapore, Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
authors.forename: José R
authors.initials: JR
authors.lastname: Dinneny
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Salzman
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058977:Molecular Sequence Annotation; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D000079962:RNA, Circular; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D018749:RNA, Plant / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D000079962:RNA, Circular; D012331:RNA, Fungal; D018749:RNA, Plant; D016053:RNA, Protozoan; D012313:RNA