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Manuscript Submission Deadline 31 December 2023
Manuscript Extension Submission Deadline 31 January 2024

Most eukaryotic genes are split by intron sequence which need to be removed by the splicing machinery from nascent pre-messenger RNAs (pre-mRNAs). The splicing process that joins the upstream 5’ splicing site (5’ ss) and downstream 3’ splicing sites (3’ ss) together is highly regulated, and can generate different transcripts from a single gene locus. High-throughput RNA sequencing has now revealed that splicing machinery can also join downstream 5’ ss to upstream 3’ ss in a process called ‘backsplicing’. Backsplicing generates circular RNAs (circRNAs) with covalently linked ends in a variety of organisms from fungi to humans. It is often facilitated by base-pairing between the flanking introns of circularized exon(s), RNA binding proteins, exon skipping events, and by the levels of core factors of splicing machinery, but the detailed mechanisms of the biogenesis of circRNA are still not fully understood. Although thousands of circRNAs have been identified by RNAseq in diverse organisms, the functional roles of most circRNAs remain largely unexplored and require further investigation.

Circular RNAs (circRNAs) are abundantly expressed in various tissues and have been implicated in several diseases such as neurodegenerative diseases, cardiovascular disease and cancer. In recent years, systems biology research has focused more on developing novel methods and algorithms to identify and characterise circRNAs, as well as evaluating synthetic circRNAs as potential therapeutics. One of the most studied circRNAs is CDR1as/ciRS7 which is highly abundant in neurons and has more than 60 evolutionary conserved miR-7 binding sites. CDR1as was originally thought to sequester miR-7 by acting as a microRNA sponge to modulate the expression of target mRNAs of miR-7. Recent CDR1as KO mouse model data suggests that the main function of CDR1as is to stabilize miR-7 and/or control its localization in neurons at a systems level. In addition to functioning as microRNA sponge, circRNAs has been reported to have diverse functions including affecting transcription/splicing and even encoding functional proteins.

The aim of this Research Topic is to collect Original Research Articles and Reviews which study and/or discuss the identification, regulation, and function of circRNAs using a system-wide approach. With this collection, we seek to improve our understanding of circRNA biogenesis and their functions in both normal physiological and disease conditions.

Areas to be covered in this Research Topic may include, but not limited to:

• Novel computational methods for circRNA identification

• circRNA networks

• Novel methods for circRNA enrichment and profiling.

• Regulation of circRNA in physiological and disease conditions.

• Function of circRNA e.g. sponging microRNA, translation etc.

• Degradation of circRNA in steady state or stress condition.

• Applications of artificial circRNAs in disease therapy

• Applications of circRNAs for therapeutic discovery

• CircRNA as biomarkers for disease.

Keywords: circular RNA, circRNA, systems biology, splicing


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Most eukaryotic genes are split by intron sequence which need to be removed by the splicing machinery from nascent pre-messenger RNAs (pre-mRNAs). The splicing process that joins the upstream 5’ splicing site (5’ ss) and downstream 3’ splicing sites (3’ ss) together is highly regulated, and can generate different transcripts from a single gene locus. High-throughput RNA sequencing has now revealed that splicing machinery can also join downstream 5’ ss to upstream 3’ ss in a process called ‘backsplicing’. Backsplicing generates circular RNAs (circRNAs) with covalently linked ends in a variety of organisms from fungi to humans. It is often facilitated by base-pairing between the flanking introns of circularized exon(s), RNA binding proteins, exon skipping events, and by the levels of core factors of splicing machinery, but the detailed mechanisms of the biogenesis of circRNA are still not fully understood. Although thousands of circRNAs have been identified by RNAseq in diverse organisms, the functional roles of most circRNAs remain largely unexplored and require further investigation.

Circular RNAs (circRNAs) are abundantly expressed in various tissues and have been implicated in several diseases such as neurodegenerative diseases, cardiovascular disease and cancer. In recent years, systems biology research has focused more on developing novel methods and algorithms to identify and characterise circRNAs, as well as evaluating synthetic circRNAs as potential therapeutics. One of the most studied circRNAs is CDR1as/ciRS7 which is highly abundant in neurons and has more than 60 evolutionary conserved miR-7 binding sites. CDR1as was originally thought to sequester miR-7 by acting as a microRNA sponge to modulate the expression of target mRNAs of miR-7. Recent CDR1as KO mouse model data suggests that the main function of CDR1as is to stabilize miR-7 and/or control its localization in neurons at a systems level. In addition to functioning as microRNA sponge, circRNAs has been reported to have diverse functions including affecting transcription/splicing and even encoding functional proteins.

The aim of this Research Topic is to collect Original Research Articles and Reviews which study and/or discuss the identification, regulation, and function of circRNAs using a system-wide approach. With this collection, we seek to improve our understanding of circRNA biogenesis and their functions in both normal physiological and disease conditions.

Areas to be covered in this Research Topic may include, but not limited to:

• Novel computational methods for circRNA identification

• circRNA networks

• Novel methods for circRNA enrichment and profiling.

• Regulation of circRNA in physiological and disease conditions.

• Function of circRNA e.g. sponging microRNA, translation etc.

• Degradation of circRNA in steady state or stress condition.

• Applications of artificial circRNAs in disease therapy

• Applications of circRNAs for therapeutic discovery

• CircRNA as biomarkers for disease.

Keywords: circular RNA, circRNA, systems biology, splicing


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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