isoCirc catalogs full-length circular RNA isoforms in human transcriptomes

Ruijiao Xin, Yan Gao, Yuan Gao, Robert Wang, Kathryn E. Kadash-Edmondson, Bo Liu, Yadong Wang, Lan Lin and Yi Xing ()
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Ruijiao Xin: Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia
Yan Gao: Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia
Yuan Gao: Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia
Robert Wang: University of Pennsylvania
Kathryn E. Kadash-Edmondson: Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia
Bo Liu: Harbin Institute of Technology
Yadong Wang: Harbin Institute of Technology
Lan Lin: University of Pennsylvania
Yi Xing: Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Circular RNAs (circRNAs) have emerged as an important class of functional RNA molecules. Short-read RNA sequencing (RNA-seq) is a widely used strategy to identify circRNAs. However, an inherent limitation of short-read RNA-seq is that it does not experimentally determine the full-length sequences and exact exonic compositions of circRNAs. Here, we report isoCirc, a strategy for sequencing full-length circRNA isoforms, using rolling circle amplification followed by nanopore long-read sequencing. We describe an integrated computational pipeline to reliably characterize full-length circRNA isoforms using isoCirc data. Using isoCirc, we generate a comprehensive catalog of 107,147 full-length circRNA isoforms across 12 human tissues and one human cell line (HEK293), including 40,628 isoforms ≥500 nt in length. We identify widespread alternative splicing events within the internal part of circRNAs, including 720 retained intron events corresponding to a class of exon-intron circRNAs (EIciRNAs). Collectively, isoCirc and the companion dataset provide a useful strategy and resource for studying circRNAs in human transcriptomes.

Date: 2021
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DOI: 10.1038/s41467-020-20459-8

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