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Review
. 2019 Aug 24;10(9):642.
doi: 10.3390/genes10090642.

Integration of Bioinformatic Predictions and Experimental Data to Identify circRNA-miRNA Associations

Martina Dori  1 , Silvio Bicciato  2
Affiliations
Review

Integration of Bioinformatic Predictions and Experimental Data to Identify circRNA-miRNA Associations

Martina Dori et al. Genes (Basel). .

Abstract

Circular RNAs (circRNAs) have recently emerged as a novel class of transcripts, characterized by covalently linked 3'-5' ends that result in the so-called backsplice junction. During the last few years, thousands of circRNAs have been identified in different organisms. Yet, despite their role as disease biomarker started to emerge, depicting their function remains challenging. Different studies have shown that certain circRNAs act as miRNA sponges, but any attempt to generalize from the single case to the "circ-ome" has failed so far. In this review, we explore the potential to define miRNA "sponging" as a more general function of circRNAs and describe the different approaches to predict miRNA response elements (MREs) in known or novel circRNA sequences. Moreover, we discuss how experiments based on Ago2-IP and experimentally validated miRNA:target duplexes can be used to either prioritize or validate putative miRNA-circRNA associations.

Keywords: circRNA; miRNA; miRNA sponge; target prediction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Linear vs Circular splicing. Circular RNAs (circRNAs) are formed from an unusual splicing event that results in covalently linked 3′–5′ ends termed as a backsplice junction (top, indicated by a red arrow). As for linear transcripts (bottom), circRNAs can undergo alternative splicing, resulting in different classes of transcripts (mono or multi exonic, intronic, exon-intron structure).
Figure 2
Figure 2
A miRNA-circRNA-mRNA network. It has been proposed that circRNA can act as a miRNA sponge, therefore competing with a linear target for the binding of the RISC complex. In the absence of circRNA, miRNAs are free to bind to their linear target, determining their repression. When the circRNA is expressed, the miRNA will guide the RISC complex to bind the circRNA, ultimately causing the de-repression of the mRNA. mRNA is depicted as an Open Reading Frame (ORF) with a 5′ cap (m7G) and a 3′ poly(A) tail.
Figure 3
Figure 3
Per year number of publication indexed in PubMed. Dark grey represents the number of publications resulting by the search term “circRNA” while light grey represents the number of papers resulting from the combined search of “circRNA miRNA”.
Figure 4
Figure 4
A possible pipeline for the comprehensive assessment of circRNA:miRNA binding sites starting from a custom set of expressed circRNA sequences (left) and a practical example on the outcome of each step on a set of randomly chosen sequences from previous work [30] (right).
See this image and copyright information in PMC

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