Cell-Type Specific Features of Circular RNA Expression

Julia Salzman,Raymond E Chen,Mari N Olsen,Patrick O Brown,Peter L Wang,John V Moran

doi:10.1371/journal.pgen.1003777

Julia Salzman, Raymond E Chen + Show 4 more

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https://doi.org/10.1371/journal.pgen.1003777

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Journal: PLoS Genetics	Publication Date: Sep 5, 2013
Citations: 1611	License type: CC BY 4.0

Affiliation: Stanford University, Howard Hughes Medical Institute

Abstract

Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA. Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific. These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.

Highlights

We were surprised to find that the predominant RNA isoform from hundreds of human genes is a circle, and that circular RNAs were transcribed from thousands of genes in both human and mouse [1]
A major challenge in bioinformatic and statistical identification of novel RNA isoforms, circular RNA, involves distinguishing bona fide evidence of scrambled exons in RNA from confounding factors such as sequence degeneracy at exon boundaries and sequencing errors. To address these challenges and to identify circular isoforms from public ENCODE RNA-Seq data, we developed a new bioinformatic approach
We reported that circular RNA isoforms, previously thought to be very rare, are a pervasive feature of eukaryotic gene expression programs; the major RNA isoform from hundreds of human genes is a circle

Summary

Introduction

We were surprised to find that the predominant RNA isoform from hundreds of human genes is a circle, and that circular RNAs were transcribed from thousands of genes in both human and mouse [1]. In the former report, a large majority of the circular isoforms we had described (1025 of 1319) were identified by deep sequencing of RNase R-treated RNA. This overlap in circles identified in these two studies is noteworthy because the more recent report focused on fibroblasts, while we previously analyzed RNA isolated from leukocytes and pediatric leukemias

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