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Updated: Nov 29, 2025

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
SRRM4 Expands the Repertoire of Circular RNAs by Regulating Microexon Inclusion
Vanessa M Conn1,2, Marta Gabryelska1,2, Shashikanth Marri1,2
1Flinders Cancer Research, College of Medicine and Public Health, Flinders University, Bedford Park 5042, South Australia, Australia.
Researchers discovered over 100,000 circular RNAs (circRNAs), including previously overlooked microexons (MEs). The splicing factor SRRM4 drives the biogenesis of novel microexon-containing circRNAs (ME-circRNAs), impacting cancer prognostics.
Area of Science:
- Non-coding RNA biology
- Bioinformatics
- Cancer genomics
Background:
- High-throughput RNA sequencing (RNA-seq) has identified over 100,000 circular RNAs (circRNAs).
- Microexons (MEs), present in 30% of mRNA transcripts, have been largely overlooked in circRNA research.
- circRNAs show potential as prognostic markers in gliomas.
Purpose of the Study:
- To identify and characterize microexon-containing circRNAs (ME-circRNAs).
- To investigate the role of the splicing factor SRRM4 in ME-circRNA biogenesis.
- To explore the clinical relevance of ME-circRNAs in glioma.
Main Methods:
- Utilized standard circRNA prediction pipelines (CIRCexplorer2, CIRI2) and a novel chimera-identification pipeline (Hyb).
- Analyzed circRNA-seq datasets from glioma tissues and matched controls.
- Overexpressed SRRM4 in HEK293 cells to study ME-circRNA generation.
Main Results:
- Identified over 2000 ME-circRNAs containing novel MEs previously uncalled by standard pipelines.
- ME-circRNA abundance in gliomas correlated with SRRM4 expression.
- SRRM4 overexpression induced over 2000 novel ME-circRNAs, including ME-circEIF4G3, and altered canonical circRNA levels.
Conclusions:
- SRRM4 is a bona fide circRNA biogenesis factor, particularly for ME-circRNAs.
- ME-circRNAs represent a newly recognized class of non-coding RNAs with implications in oncogenesis.
- ME-circRNAs and SRRM4 hold potential as prognostic biomarkers for glioma stratification.
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