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Title:
Expanded identification and characterization of mammalian circular RNAs | Genome Biology
Description:
Background The recent reports of two circular RNAs (circRNAs) with strong potential to act as microRNA (miRNA) sponges suggest that circRNAs might play important roles in regulating gene expression. However, the global properties of circRNAs are not well understood. Results We developed a computational pipeline to identify circRNAs and quantify their relative abundance from RNA-seq data. Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from the ENCODE project, we annotated 7,112 human circRNAs that were estimated to comprise at least 10% of the transcripts accumulating from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, but they are no more cell-type-specific than are mRNAs with similar overall expression levels. Although most circRNAs overlap protein-coding sequences, ribosome profiling provides no evidence for their translation. We also annotated 635 mouse circRNAs, and although 20% of them are orthologous to human circRNAs, the sequence conservation of these circRNA orthologs is no higher than that of their neighboring linear exons. The previously proposed miR-7 sponge, CDR1as, is one of only two circRNAs with more miRNA sites than expected by chance, with the next best miRNA-sponge candidate deriving from a gene encoding a primate-specific zinc-finger protein, ZNF91. Conclusions Our results provide a new framework for future investigation of this intriguing topological isoform while raising doubts regarding a biological function of most circRNAs.
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Keywords {π}
circrnas, circular, circrna, figure, pubmed, human, mirna, reads, cell, additional, article, data, exons, sites, file, rnaseq, linear, mouse, cas, google, scholar, fractions, isoforms, junctions, gene, cdras, conserved, analysis, expression, central, rnas, fraction, cells, splicing, found, genome, types, sequence, conservation, donor, acceptor, genes, catalog, nonpolyaselected, neighboring, rna, distribution, observed, results, compared,
Topics {βοΈ}
primate-specific zinc-finger protein paired-end rna-seq data gt-ag-flanking candidates tended gt-ag-flanking candidates falling long-read rna-seq data article download pdf duplication-aware phylogenetic trees back-spliced junction-spanning reads multi-exon genes generate rna-seq reads arising sequence-dependent noncoding functions paired mann-whitney test repeat-rich coding regions largely inert side-products selected rna-seq data testis-determining gene sry rna-seq reads spanning protein-coding sequences raised inert splicing side-products removing pcr-duplicated reads mirna-loaded argonaute proteins gt-ag-flanking junctions gt-ag-flanking candidates identified trans-spliced event trans-splicing rarely contributed ago2-crosslinking clusters assigned imperfect pre-mrna splicing sequence-dependent biological function related subjects selected rna-seq datasets distinguish trans-spliced products carnitine octanoyltransferase pre-mrnas gt-ag splicing signals annotated protein-coding genes c2h2 zinc finger total junction-spanning reads protein-coding-independent conservation mirna-sponge candidate deriving refseq-annotated linear junctions produce trans-spliced isoforms circular junction-spanning reads cell-type-specific manner cell-type specific features select control k-mers long noncoding rnas gencode-annotated ncrna genes triggers endonucleolytic cleavage mirna site search junction-spanning reads mapped cell-type-specificity scores
Questions {β}
- What about functional potential of the other 7,000-plus circRNAs?
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headline:Expanded identification and characterization of mammalian circular RNAs
description:The recent reports of two circular RNAs (circRNAs) with strong potential to act as microRNA (miRNA) sponges suggest that circRNAs might play important roles in regulating gene expression. However, the global properties of circRNAs are not well understood. We developed a computational pipeline to identify circRNAs and quantify their relative abundance from RNA-seq data. Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from the ENCODE project, we annotated 7,112 human circRNAs that were estimated to comprise at least 10% of the transcripts accumulating from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, but they are no more cell-type-specific than are mRNAs with similar overall expression levels. Although most circRNAs overlap protein-coding sequences, ribosome profiling provides no evidence for their translation. We also annotated 635 mouse circRNAs, and although 20% of them are orthologous to human circRNAs, the sequence conservation of these circRNA orthologs is no higher than that of their neighboring linear exons. The previously proposed miR-7 sponge, CDR1as, is one of only two circRNAs with more miRNA sites than expected by chance, with the next best miRNA-sponge candidate deriving from a gene encoding a primate-specific zinc-finger protein, ZNF91. Our results provide a new framework for future investigation of this intriguing topological isoform while raising doubts regarding a biological function of most circRNAs.
datePublished:2014-07-29T00:00:00Z
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miRNA Family
miRNA Sponge
Orthologous Exon
Neighboring Exon
miRNA Site
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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headline:Expanded identification and characterization of mammalian circular RNAs
description:The recent reports of two circular RNAs (circRNAs) with strong potential to act as microRNA (miRNA) sponges suggest that circRNAs might play important roles in regulating gene expression. However, the global properties of circRNAs are not well understood. We developed a computational pipeline to identify circRNAs and quantify their relative abundance from RNA-seq data. Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from the ENCODE project, we annotated 7,112 human circRNAs that were estimated to comprise at least 10% of the transcripts accumulating from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, but they are no more cell-type-specific than are mRNAs with similar overall expression levels. Although most circRNAs overlap protein-coding sequences, ribosome profiling provides no evidence for their translation. We also annotated 635 mouse circRNAs, and although 20% of them are orthologous to human circRNAs, the sequence conservation of these circRNA orthologs is no higher than that of their neighboring linear exons. The previously proposed miR-7 sponge, CDR1as, is one of only two circRNAs with more miRNA sites than expected by chance, with the next best miRNA-sponge candidate deriving from a gene encoding a primate-specific zinc-finger protein, ZNF91. Our results provide a new framework for future investigation of this intriguing topological isoform while raising doubts regarding a biological function of most circRNAs.
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miRNA Family
miRNA Sponge
Orthologous Exon
Neighboring Exon
miRNA Site
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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