Genome-wide analysis of Drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation Journal Article


Authors: Westholm, J. O.; Miura, P.; Olson, S.; Shenker, S.; Joseph, B.; Sanfilippo, P.; Celniker, S. E.; Graveley, B. R.; Lai, E. C.
Article 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. Westholm etal. annotate Drosophila circular RNAs from a massive collection of total RNA-seq data, providing insights into their biogenesis and function. In particular, circularizing exons are predominantly associated with long flanking introns, are preferred locations of conserved coding miRNA sites, and accumulate to highest levels in the aging CNS.
Keywords: adult; controlled study; unclassified drug; exon; nonhuman; animal tissue; microrna; intron; central nervous system; rna; genome analysis; aging; dna flanking region; rna structure; rna splicing; rna sequence; tissue specificity; polyadenylic acid; article; nucleotide motif; circular rna; drosophila mojavensis
Journal Title: Cell Reports
Volume: 9
Issue: 5
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2014-12-11
Start Page: 1966
End Page: 1981
Language: English
DOI: 10.1016/j.celrep.2014.10.062
PROVIDER: scopus
PMCID: PMC4279448
PUBMED: 25544350
DOI/URL:
Notes: Export Date: 2 January 2015 -- Source: Scopus
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MSK Authors
  1. Eric C Lai
    153 Lai
  2. Pedro Edward Taiyo Miura
    6 Miura
  3. Brian Jude Joseph
    9 Joseph