Abstract

MicroRNAs have established their role as potent regulators of the epigenome. Interestingly, most miRNAs are located within protein-coding genes with functional consequences that have yet to be fully investigated. MiRIAD is a database with an interactive and user-friendly online interface that has been facilitating research on intragenic miRNAs. In this article, we present a major update. First, data for five additional species (chimpanzee, rat, dog, cow and frog) were added to support the exploration of evolutionary aspects of the relationship between host genes and intragenic miRNAs. Moreover, we integrated data from two different sources to generate a comprehensive alternative polyadenylation dataset. The miRIAD interface was therefore redesigned and provides a completely new gene model representation, including an interactive visualization of the 3′ untranslated region (UTR) with alternative polyadenylation sites, corresponding signals and potential miRNA binding sites. Furthermore, we expanded on functional host gene network analysis. Although the previous version solely reported protein interactions, the update features a separate network analysis view that can either be accessed through the submission of a list of genes of interest or directly from a gene’s list of protein interactions. In addition to statistical properties of the submitted gene set, the interaction network graph is presented and miRNAs with seed site over- and underrepresentation are identified. In summary, the update of miRIAD provides novel datasets and bioinformatics resources with a significant increase in functionality to facilitate intragenic miRNA research in a user-friendly and interactive way. Database URL: http://www.miriad-database.org

Highlights

  • MiRNAs are well-known as small molecules that are involved in controlling regulatory networks of the gene expression [1]

  • Investigating the distribution across tissues in human, we found that host genes of intragenic miRNAs are predominantly expressed in neuronal tissue and testis across all organisms (Figure 1B)

  • 94.6% of human host genes have annotated alternative polyadenylation (APA) sites, which is more than expected compared with 83% of all human genes (P value 1⁄4 4.6e-38, Fisher exact test)

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Summary

Introduction

MiRNAs are well-known as small molecules that are involved in controlling regulatory networks of the gene expression [1]. Recent research suggests evolutionary implications of intragenic miRNA development [14, 15], yielding that novel miRNAs seem to benefit from intragenic colocalization by utilizing existing regulatory circuitries of their host genes [14]. Increasing evidence highlights the importance of the role of alternative polyadenylation (APA) to characterize the relationship between intragenic miRNAs and their host genes [5, 6]. These novel discoveries prompted us to develop a major update of the miRIAD database and interface to account for these new aspects of intragenic miRNA–host gene relationship

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