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Updated: May 28, 2025

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Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
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Past, present, and future strategies for detecting and quantifying circular RNA variants.
He Lin1, Vanessa M Conn1, Simon J Conn1
1Flinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Adelaide, Australia.
The FEBS Journal
|February 11, 2025
Summary
Circular RNAs (circRNAs) are unique RNA molecules detected using advanced sequencing. New methods improve their sensitive detection and quantification in biological samples.
Area of Science:
- Molecular Biology
- Genomics
- RNA Biology
Background:
- Circular RNAs (circRNAs) are covalently closed RNA transcripts formed by backsplicing.
- Despite being ubiquitous, circRNAs were historically difficult to detect due to their unique structure.
- Over 3 million unique circRNA transcripts have been identified recently.
Purpose of the Study:
- To review advancements in detecting and quantifying circRNAs.
- To highlight next-generation sequencing (NGS) approaches for circRNA variant detection.
- To discuss accurate normalization methods for circRNA quantification.
Main Methods:
- Review of existing literature on circRNA detection and quantification.
- Focus on next-generation sequencing (NGS) strategies.
- Discussion of bioinformatics pipelines and long-read sequencing.
Main Results:
- CircRNAs are cell type-specific, stable, and often conserved.
- Low expression levels and complex structures challenge accurate detection.
- NGS, enrichment, and specialized bioinformatics are crucial for comprehensive characterization.
Conclusions:
- Specific and ultrasensitive detection methods are essential for circRNA research.
- Advancements in sequencing technologies are critical for identifying circRNA variants.
- Accurate quantification and normalization are key for understanding circRNA function in biological samples.

