FUCHS—towards full circular RNA characterization using RNAseq

Abstract

Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. A downstream 5′ splice site is linked to an upstream 3′ splice site to form a circular transcript instead of a canonical linear transcript. Recent advances in next-generation sequencing (NGS) have brought circRNAs back into the focus of many scientists. Since then, several studies reported that circRNAs are differentially expressed across tissue types and developmental stages, implying that they are actively regulated and not merely a by-product of splicing. Though functional studies have shown that some circRNAs could act as miRNA-sponges, the function of most circRNAs remains unknown. To expand our understanding of possible roles of circular RNAs, we propose a new pipeline that could fully characterizes candidate circRNA structure from RNAseq data—FUCHS: FUll CHaracterization of circular RNA using RNA-Sequencing. Currently, most computational prediction pipelines use back-spliced reads to identify circular RNAs. FUCHS extends this concept by considering all RNA-seq information from long reads (typically >150 bp) to learn more about the exon coverage, the number of double break point fragments, the different circular isoforms arising from one host-gene, and the alternatively spliced exons within the same circRNA boundaries. This new knowledge will enable the user to carry out differential motif enrichment and miRNA seed analysis to determine potential regulators during circRNA biogenesis. FUCHS is an easy-to-use Python based pipeline that contributes a new aspect to the circRNA research.

Profiling and functional analysis of circular RNAs in acute promyelocytic leukemia and their dynamic regulation during all-trans retinoic acid treatment

“…Yet, another important extension of our work would be to elaborate on the internal structure of circRNAs, including the exact exon compositions and alternative splicing events. Several pipelines or algorithms, for example, CIRI-AS 48 , RAISE 49 , and FUCHS 50 , are now available for the high-throughput detection of the internal components of circRNAs. Further, exploration of the internal structures of circRNAs will enrich our understanding on the functional roles of circRNAs in APL.…”

Circular RNA expression profiles reveal that hsa_circ_0018289 is up-regulated in cervical cancer and promotes the tumorigenesis

“…Presently, the role and mechanism of circRNAs in tumor progression are still not well identified [ 15 ]. Although circRNAs have been discovered for decades, the significance of circRNAs is recognized with the developing of high-throughput RNA-sequencing (RNA-Seq) and bioinformatics analysis [ 16 , 17 ]. Emerging evidences have illustrated that circRNAs play important role in multiple physiological and pathological functions, involving cardiovascular system disease, nervous system disease and series of tumors [ 18 – 20 ].…”

RNA-seq reveals the circular RNA and miRNA expression profile of peripheral blood mononuclear cells in patients with rheumatoid arthritis

“…CircRNAs are an important class of widespread endogenous noncoding RNAs that may play important roles in diseases by regulating gene expression processes, such as transcription, splicing and translation [6,7]. Recently, there is accumulating evidence that circRNAs are abundant in mammals and function as molecular sponges for their target miRNAs to regulate gene expression.…”