Biogenesis, identification, and function of exonic circular RNAs

Area of Science:

• Molecular Biology
• Genomics
• RNA Biology

Background:

• Circular RNAs (circRNAs) are RNA molecules formed by covalent binding, previously considered splicing by-products.
• Advances in RNA sequencing have renewed interest in exonic circRNAs (ecircRNAs), revealing their abundance and conservation.
• The biogenesis and functions of ecircRNAs are largely unknown but show potential for diagnostic applications.

Purpose of the Study:

• To review the biogenesis, identification, properties, and function of exonic circRNAs (ecircRNAs).
• To discuss challenges in ecircRNA detection and evaluation of current detection methods.
• To highlight unanswered questions and future research directions in the field of circRNAs.

Main Methods:

• Analysis of high-throughput RNA sequencing (RNA-seq) data for nonco-linear (NCL) RNA identification.
• Review of existing literature on circRNA biogenesis, properties, and functions.
• Evaluation of the accuracy (sensitivity and precision) of established circRNA detection tools.

Main Results:

• Thousands of ecircRNAs have been identified across diverse species and tissues using RNA-seq.
• ecircRNAs exhibit potential roles in microRNA regulation, gene transcription, cell proliferation, and RNA-binding protein interactions.
• Significant challenges exist in accurately detecting ecircRNAs, including distinguishing them from other NCL RNAs and mitigating sequencing/alignment errors.

Conclusions:

• ecircRNAs represent a promising class of molecules with potential as diagnostic biomarkers.
• Further research is needed to overcome detection challenges and fully elucidate the functional roles of ecircRNAs.
• Standardization of bioinformatics methods and rigorous validation are crucial for advancing ecircRNA research.