Abstract
Circular RNAs are new players in regulation of post transcriptional gene expression. Animal genomes express many circular RNAs from diverse genomic locations. A recent study has validated a fairly large number of circular RNAs in human, mouse, and nematode. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation. In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes. We carried out gene ontology (GO) enrichment analysis on the set of protein coding genes in the miRNA- circRNA interactome of individual diseases to check the enrichment of genes associated with particular biological processes. Secondly, disease associated SNPs were mapped on circRNA loci, and Argonaute (Ago) interaction sites on circular RNAs were identified. We compiled a database of disease-circRNA association in Circ2Traits (http://gyanxet-beta.com/circdb/), the first comprehensive knowledgebase of potential association of circular RNAs with diseases in human.
Highlights
Circular RNAs, formed by covalent linkage of the ends of a single RNA molecule, are newly discovered RNAs that sponge miRNAs to block their function (Memczak et al, 2013)
We implemented a measure for showing the likelihood of a circular RNAs (circRNA) to be associated with a disease in terms of the significance of the circRNA’s interaction with miRNAs associated with the concerned disease
DISCUSSION circRNAs, stable transcripts expressed from diverse genomic locations, are recently identified as important players in regulation of cellular miRNA abundance and are a major component in the miRNA-mediated post transcriptional regulatory network
Summary
Circular RNAs, formed by covalent linkage of the ends of a single RNA molecule, are newly discovered RNAs that sponge miRNAs to block their function (Memczak et al, 2013). These circular transcripts were previously thought to be scarcely expressed until recently, when thousands of circular RNA transcripts were identified in both human and mouse by two independent studies by Jeck et al (2013) and Memczak et al (2013). Memczak et al have identified 2000 human, 1900 mouse, and 700 nematode circular RNAs from sequencing data (Memczak et al, 2013).
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