title: Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation.
abstract: Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues, and cultured cells, to rigorously annotate >2,500 fruit fly circular RNAs. These mostly derive from back-splicing of protein-coding genes and lack poly(A) tails, and the circularization of hundreds of genes is conserved across multiple Drosophila species. We elucidate structural and sequence properties of Drosophila circular RNAs, which exhibit commonalities and distinctions from mammalian circles. Notably, Drosophila circular RNAs harbor >1,000 well-conserved canonical miRNA seed matches, especially within coding regions, and coding conserved miRNA sites reside preferentially within circularized exons. Finally, we analyze the developmental and tissue specificity of circular RNAs and note their preferred derivation from neural genes and enhanced accumulation in neural tissues. Interestingly, circular isoforms increase substantially relative to linear isoforms during CNS aging and constitute an aging biomarker.
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA.
authors.forename: Jakub O
authors.initials: JO
authors.lastname: Westholm
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Department of Biology, University of Nevada, Reno, Nevada 89557, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Miura
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT 06032, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Olson
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Tri-Institutional Program in Computational Biology and Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Sol
authors.initials: S
authors.lastname: Shenker
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Gerstner Sloan-Kettering Graduate Program of Biomedical Sciences, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Joseph
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Gerstner Sloan-Kettering Graduate Program of Biomedical Sciences, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: Piero
authors.initials: P
authors.lastname: Sanfilippo
authors.affiliation: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94701, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT 06032, USA.
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA. Electronic address: laie@mskcc.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D049750:Genome, Insect; D008297:Male; D009417:Nerve Tissue / Q000378:metabolism*; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D000079962:RNA, Circular; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D000079962:RNA, Circular; D012313:RNA