Related Experiment Video
Updated: Feb 6, 2026

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
Circular RNAs and competing endogenous RNA (ceRNA) networks
Apratim Mitra1, Karl Pfeifer1, Ki-Sun Park1
1Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health, and Human Development, National Institutes of Health, Bethesda, MD, USA.
This study explores the role of circular RNAs (circRNAs) in gene regulation. Using bioinformatics tools, researchers found that circRNAs are expressed in a cell type-specific manner and are conserved across species. These findings suggest that circRNAs may have functional roles rather than being random byproducts of splicing. The study focuses on the possibility that circRNAs act as part of ceRNA networks by binding to microRNAs (miRNAs), which could influence gene expression. The researchers observed that circRNA-miRNA interactions vary in different conditions, including cancer models. These results support the idea that circRNAs may play a regulatory role in both normal development and disease processes.
Area of Science:
- Non-coding RNA biology within molecular genetics
- RNA regulatory networks in developmental biology
Background:
Understanding RNA regulation has become central to molecular biology. While messenger RNA was once considered the sole functional RNA, recent discoveries have revealed non-coding RNAs as key regulators. Circular RNAs (circRNAs) have emerged as a distinct class with unique structural properties. These molecules are formed through back-splicing events, a process distinct from linear RNA formation. Their presence in multiple cell types indicates potential functional roles. However, the precise mechanisms remain unclear in many cases. Prior research has shown that circRNAs can be conserved across species, suggesting evolutionary importance. Despite these findings, the specific regulatory roles of circRNAs are still being explored.
Purpose Of The Study:
This study aims to clarify the functional relevance of circRNAs by examining their role in regulatory networks. The focus is on competing endogenous RNA (ceRNA) interactions, where circRNAs may act as molecular sponges. Researchers are particularly interested in how these interactions influence gene expression. The goal is to determine if circRNAs contribute to normal developmental processes. Additionally, the study seeks to explore their involvement in disease states like cancer. By analyzing ceRNA networks, the authors aim to uncover new regulatory mechanisms. The study also addresses the need for a better understanding of circRNA expression patterns. This work contributes to the broader field of RNA-mediated gene regulation.
Main Methods:
The researchers employed bioinformatics tools to analyze circRNA expression data. They used RNA sequencing datasets from various cell types to identify circRNA profiles. Computational algorithms helped detect potential ceRNA interactions. The study compared circRNA sequences across species to assess conservation. Expression levels were evaluated under different developmental and pathological conditions. Statistical models were applied to determine correlations between circRNAs and miRNAs. The team validated findings using experimental techniques like qPCR and RNA immunoprecipitation. These methods provided insights into the functional potential of circRNAs.
Main Results:
The analysis revealed that circRNAs exhibit cell type-specific expression patterns. Many circRNAs were found to be conserved across species, suggesting evolutionary significance. The study identified several circRNAs that bind to microRNAs (miRNAs) with high affinity. These interactions imply that circRNAs may act as miRNA sponges in ceRNA networks. The researchers observed that circRNA-miRNA interactions vary under different physiological conditions. In cancer models, certain circRNAs showed altered expression levels compared to healthy cells. These findings suggest a potential role for circRNAs in disease progression. The results support the hypothesis that circRNAs contribute to RNA regulatory networks.
Conclusions:
The study suggests that circRNAs may function as part of ceRNA regulatory networks. These networks appear to influence gene expression by modulating miRNA activity. The findings support the idea that circRNAs are not merely byproducts of splicing. Instead, they may have active roles in cellular regulation. The authors propose that circRNAs could serve as biomarkers or therapeutic targets in disease contexts. However, the exact mechanisms remain to be fully elucidated. The study highlights the need for further experimental validation of predicted interactions. These conclusions align with the authors' emphasis on the functional potential of circRNAs.
Frequently Asked Questions
The authors propose that circRNAs function as miRNA sponges in ceRNA networks, modulating gene expression.
CircRNAs are formed through back-splicing, resulting in covalently closed loops without 5' or 3' ends.
Conservation suggests evolutionary pressure to maintain circRNA sequences, implying functional relevance.
MiRNAs bind to circRNAs, which may compete for miRNA binding sites on target mRNAs, altering gene expression.
RNA sequencing datasets from multiple cell types were used to profile circRNA expression patterns.
The authors suggest that altered circRNA expression in cancer models may contribute to disease progression.
Related Concept Videos
siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
piRNA - Piwi-interacting RNAs
lncRNA - Long Non-coding RNAs
Ribosomal RNA Synthesis
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
RNA Polymerase II Accessory Proteins

