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Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types

Julia SalzmanDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of AmericaCharles GawadDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of AmericaPeter Lincoln WangDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of AmericaNorman J. LacayoDepartment of Pediatric Hematology/Oncology, Stanford University School of Medicine, Stanford, California, United States of AmericaPatrick O. BrownDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America
2012en
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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.

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