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

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 widespread and perhaps general feature of the gene expression program in human cells. Overall design: 3 samples of non-malignant primary human leukocytes, one replicate each