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PMID: 22319583 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types.

PloS one ·Vol. 7 ·No. 2 ·2012-00-00 ·Pages e30733

Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO

Abstract

Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.

MeSH Terms

Base Sequence Exons Gene Expression Humans Protein Isoforms RNA/genetics RNA Precursors/genetics RNA Splicing RNA, Circular

Chemicals

Protein Isoforms RNA Precursors RNA, Circular RNA

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Salzman Julia

Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.

Gawad Charles

Wang Peter Lincoln

Lacayo Norman

Brown Patrick O

References (28)

28 references, click to expand

A circularized sodium-calcium exchanger exon 2 transcript.
J Biol Chem. 1999 Mar 19;274(12):8153-60 PMID: 10075718
Bioinformatic analysis of exon repetition, exon scrambling and trans-splicing in humans.
Bioinformatics. 2006 Mar 15;22(6):692-8 PMID: 16308355
Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs.
Science. 1995 Apr 21;268(5209):415-7 PMID: 7536344
Exon scrambling of MLL transcripts occur commonly and mimic partial genomic duplication of the gene.
Gene. 1998 Feb 27;208(2):167-76 PMID: 9540777
Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk.
PLoS Genet. 2010 Dec 02;6(12):e1001233 PMID: 21151960
Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells.
Nature. 1979 Jul 26;280(5720):339-40 PMID: 460409
Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing.
Hum Mol Genet. 1999 Mar;8(3):493-500 PMID: 9949208
Expression of a linear Sry transcript in the mouse genital ridge.
Nat Genet. 1995 Aug;10(4):480-2 PMID: 7670499
ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.
PLoS Biol. 2011 Sep;9(9):e1001156 PMID: 21949640
First come, first served revisited: factors affecting the same alternative splicing event have different effects on the relative rates of intron removal.
RNA. 2010 May;16(5):904-12 PMID: 20357345
miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA.
EMBO J. 2011 Sep 30;30(21):4414-22 PMID: 21964070
Noncanonical RNAs from transcripts of the Drosophila muscleblind gene.
J Hered. 2006 May-Jun;97(3):253-60 PMID: 16714427
Expression of the mouse testis-determining gene Sry in male preimplantation embryos.
Mol Reprod Dev. 1995 Feb;40(2):196-204 PMID: 7766412
In vitro generation of a circular exon from a linear pre-mRNA transcript.
Nucleic Acids Res. 1996 Apr 1;24(7):1260-6 PMID: 8614628
A 3' consensus splice mutation in the human dystrophin gene detected by a screening for intra-exonic deletions.
Hum Mol Genet. 1992 Aug;1(5):345-6 PMID: 1303213
Post-transcriptional exon shuffling events in humans can be evolutionarily conserved and abundant.
Genome Res. 2011 Nov;21(11):1788-99 PMID: 21948523
Circular transcripts of the testis-determining gene Sry in adult mouse testis.
Cell. 1993 Jun 4;73(5):1019-30 PMID: 7684656
A coding-independent function of gene and pseudogene mRNAs regulates tumour biology.
Nature. 2010 Jun 24;465(7301):1033-8 PMID: 20577206
Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6536-41 PMID: 8692851
Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis.
Mol Cell Biol. 1997 Jun;17(6):2985-93 PMID: 9154796
Genomewide characterization of non-polyadenylated RNAs.
Genome Biol. 2011;12(2):R16 PMID: 21324177
Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing.
Nucleic Acids Res. 2006 May 08;34(8):e63 PMID: 16682442
Scrambled exons.
Cell. 1991 Feb 8;64(3):607-13 PMID: 1991322
During in vivo maturation of eukaryotic nuclear mRNA, splicing yields excised exon circles.
Nucleic Acids Res. 1996 Mar 15;24(6):1015-9 PMID: 8604331
Splicing with inverted order of exons occurs proximal to large introns.
EMBO J. 1992 Mar;11(3):1095-8 PMID: 1339341
A genome-wide survey demonstrates widespread non-linear mRNA in expressed sequences from multiple species.
Nucleic Acids Res. 2005 Oct 19;33(18):5904-13 PMID: 16237125
Expression of Sry, the mouse sex determining gene.
Development. 1995 Jun;121(6):1603-14 PMID: 7600978
Mis-splicing yields circular RNA molecules.
FASEB J. 1993 Jan;7(1):155-60 PMID: 7678559

Article Info

Journal

PloS one

Abbr.

PLoS One

ISSN

1932-6203

DOI

10.1371/journal.pone.0030733

Published

2012-00-00

Epub

2012-00-01

Pages

e30733

Language

English

Region

United States

NLM ID

101285081

PMCID

PMC3270023

Subset

Grants

Howard Hughes Medical Institute · United States

External Links

PubMed source DOI: 10.1371/journal.pone.0030733 PMC Full Text View journal details

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Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types.

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