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Updated: Sep 9, 2025

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
Prediction of Circular RNA Secondary Structures and Their Targets.
Stephan H Bernhart1, Jörg Fallmann2, Ronny Lorenz2,3
1Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, Leipzig University, Leipzig, Germany. berni@bioinf.uni-leipzig.de.
Circular RNAs (circRNAs) share structural similarities with linear RNAs, allowing similar dynamic programming solutions for folding. However, aligning circRNA sequences presents unique challenges compared to linear RNA.
Area of Science:
- Biochemistry
- Bioinformatics
- Molecular Biology
Background:
- Circular RNAs (circRNAs) exhibit unique structural properties distinct from linear RNAs.
- Understanding circRNA secondary structure is crucial for elucidating their biological functions.
- Existing computational tools primarily focus on linear RNA analysis.
Purpose of the Study:
- To compare the secondary structure prediction and alignment of circular RNAs (circRNAs) with linear RNAs.
- To review available software tools, particularly from the ViennaRNA package, for circRNA analysis.
- To highlight recent advancements in circRNA research, including chemical probing and interaction-based structure prediction.
Main Methods:
- Dynamic programming algorithms for RNA secondary structure prediction.
- Comparative analysis of sequence alignment algorithms for circular versus linear RNA.
- Review of computational tools within the ViennaRNA package.
- Discussion of experimental methods like chemical probing.
Main Results:
- Circular RNAs share fundamental folding principles (base pairing, stacking, loop entropy) with linear RNAs, enabling similar dynamic programming approaches.
- Pairwise and multiple sequence alignment for circRNAs is computationally more challenging than for linear RNAs.
- The ViennaRNA package offers solutions for circRNA structure analysis, though alignment tools are less developed.
- Recent developments include chemical probing applications and predicting structures of circRNA interactions.
Conclusions:
- Computational approaches for circRNA secondary structure prediction are analogous to those for linear RNAs.
- Sequence alignment remains a significant challenge for circular RNAs, with limited software solutions.
- Further development of bioinformatics tools is needed for comprehensive circRNA analysis and understanding their interactions.
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