Quantifying full-length circular RNAs in cancer

Circular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction po...

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Bibliographic Details
Published in:Genome research 2021-12, Vol.31 (12), p.2340-2353
Main Authors: Yu, Ken Hung-On, Shi, Christina Huan, Wang, Bo, Chow, Savio Ho-Chit, Chung, Grace Tin-Yun, Lung, Raymond Wai-Ming, Tan, Ke-En, Lim, Yat-Yuen, Tsang, Anna Chi-Man, Lo, Kwok-Wai, Yip, Kevin Y
Format: Article
Language:English
Subjects:
Alternative splicing
Computer applications
Isoforms
Method
miRNA
Nasopharyngeal carcinoma
Nasopharynx
Regulatory sequences
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Summary:Circular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction potentials. The study of circRNA function thus requires knowledge of complete circRNA sequences. Here we describe psirc, a method that can identify full-length circRNA isoforms and quantify their expression levels from RNA sequencing data. We confirm the effectiveness and computational efficiency of psirc using both simulated and actual experimental data. Applying psirc on transcriptome profiles from nasopharyngeal carcinoma and normal nasopharynx samples, we discover and validate circRNA isoforms differentially expressed between the two groups. Compared with the assumed circular isoforms derived from linear transcript annotations, some of the alternatively spliced circular isoforms have 100 times higher expression and contain substantially fewer microRNA response elements, showing the importance of quantifying full-length circRNA isoforms.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.275348.121