Expanded identification and characterization of mammalian circular RNAs

Expanded identification and characterization of mammalian circular RNAs

2014 | Junjie U Guo, Vikram Agarwal, Huili Guo, and David P Bartel
This study expands the catalog of mammalian circular RNAs (circRNAs) by developing a computational pipeline to identify and quantify circRNAs from RNA-seq data. The pipeline was applied to non-poly(A)-selected RNA-seq data from the ENCODE project, resulting in the annotation of 7,112 human circRNAs, which are estimated to comprise at least 10% of transcripts from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, and they are no more cell-type-specific than mRNAs with similar overall expression levels. Ribosome profiling provided no evidence for translation of circRNAs. The study also annotated 635 mouse circRNAs, finding that 20% are orthologous to human circRNAs, but sequence conservation is no higher than that of neighboring linear exons. The miR-7 sponge, CDR1as, is identified as one of only two circRNAs with more miRNA sites than expected by chance, with another candidate derived from a primate-specific zinc-finger protein, ZNF91. The findings suggest that most circRNAs may be inconsequential side-products of imperfect pre-mRNA splicing, rather than having significant biological functions.This study expands the catalog of mammalian circular RNAs (circRNAs) by developing a computational pipeline to identify and quantify circRNAs from RNA-seq data. The pipeline was applied to non-poly(A)-selected RNA-seq data from the ENCODE project, resulting in the annotation of 7,112 human circRNAs, which are estimated to comprise at least 10% of transcripts from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, and they are no more cell-type-specific than mRNAs with similar overall expression levels. Ribosome profiling provided no evidence for translation of circRNAs. The study also annotated 635 mouse circRNAs, finding that 20% are orthologous to human circRNAs, but sequence conservation is no higher than that of neighboring linear exons. The miR-7 sponge, CDR1as, is identified as one of only two circRNAs with more miRNA sites than expected by chance, with another candidate derived from a primate-specific zinc-finger protein, ZNF91. The findings suggest that most circRNAs may be inconsequential side-products of imperfect pre-mRNA splicing, rather than having significant biological functions.
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