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

By Julia Salzman, Charles Gawad, Peter L Wang, Norman J. Lacayo, Patrick O. Brown. PLoS ONE, 2012

2,326 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ec00a67805e2e18dc33b8f0f07472793727a1d1d

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Citations in the corpus

Translating RNA sequencing into clinical diagnostics: opportunities and challenges (2016, background): “Circular RNAs ( circRNAs) were recently rediscovered in RNA-seq experiments searching for chromosomal rearrangements in cancer 65 .”
Circular RNA: A new star of noncoding RNAs. (2015, background): “However, with the development of highthroughput sequencing technology and computational analysis, thousands of circRNAs across species from Archaea to humans have been discovered [10–16,38].”
Genomewide analysis of Drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation (2014, neutral): “Altogether, recent studies reveal a plethora of RNA circles in bacterial and metazoan species (Danan et al., 2012; Guo et al., 2014; Memczak et al., 2013; Salzman et al., 2012, 2013).”
Circular RNA: metabolism, functions and interactions with proteins (2020, background): “CircRNAs formed from exons are generally localized to the cytoplasm [41].”
Short intronic repeat sequences facilitate circular RNA production (2014, background): “Deep sequencing of the transcriptomes of numerous human cell lines, including HEK293, HeLa, and H1 human embryonic stem cells (hESCs), revealed exon–exon junction reads connecting the 39 end of exon 3 to the 59 end of exon 2 (Salzman et al. 2012; Jeck et al. 2013; Memczak et al. 2013).”
Complementary sequence-mediated exon circularization. (2014, background): “We found that multiple circularized exons could be produced from a single gene locus (Figures 1E, 6A, and 6B), and this phenomenon has also been indicated in some other genes (Burd et al., 2010; Jeck et al., 2013; Salzman et al., 2012).”
The bioinformatics toolbox for circRNA discovery and analysis (2020, background): “Due to the limited data available, this review will only cover identification or profiling tools based on RNA-Seq datasets (see Table 1).”
Using circular RNA as a novel type of biomarker in the screening of gastric cancer. (2015, methodology): “CircRNAs are widely expressed in human cells, and their expression levels can be 10-fold or higher compared to their linear isomers [10, 21].”