IsoCirc Catalogs Full-length Circular RNA Isoforms in Human Transcriptomes

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 13

PMID 33436621

Citations 68

Authors

Ruijiao Xin

Yan Gao

Yuan Gao

Robert Wang

Kathryn E Kadash-Edmondson

Bo Liu

Yadong Wang

Lan Lin

Yi Xing

Affiliations

Soon will be listed here.

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.

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