Abstract
MicroRNAs play a key role in the regulation of gene expression. A majority of microRNA–mRNA interactions remain unidentified. Despite extensive research, our ability to predict human microRNA-mRNA interactions using computational algorithms remains limited by a complexity of the models for non-canonical interactions, and an abundance of false-positive results. Here, we present the landscape of human microRNA–mRNA interactions derived from comprehensive analysis of HEK293 and Huh7.5 datasets, along with publicly available microRNA and mRNA expression data. We show that, while only 1–2% of human genes were the most regulated by microRNAs, few cell line–specific RNAs, including EEF1A1 and HSPA1B in HEK293 and AFP, APOB, and MALAT1 genes in Huh7.5, display substantial “sponge-like” properties. We revealed a group of microRNAs that are expressed at a very high level, while interacting with only a few mRNAs, which, indeed, serve as their specific expression regulators. In order to establish reliable microRNA-binding regions, we collected and systematically analyzed the data from 79 CLIP datasets of microRNA-binding sites. We report 46,805 experimentally confirmed mRNA–miRNA duplex regions. Resulting dataset is available at http://score.generesearch.ru/services/mirna/. Our study provides initial insight into the complexity of human microRNA–mRNA interactions.
Highlights
MicroRNAs are small noncoding RNAs that associate with Argonaute (AGO) protein to form a silencing complex, which regulates a gene expression (Jonas and Izaurralde, 2015)
For 36 interactions, the transforming of their coordinates failed and, in total, we revealed 18,478 microRNA–mRNA interactions in 22,030 genome regions
The sets of microRNA–mRNA interactions retrieved in HEK293 and in Huh7.5 by CLASH (Helwak et al, 2013) and CLEAR-cross-linking with immunoprecipitation (CLIP) (Moore et al, 2015) protocols were compared, respectively, to hg19 genome references
Summary
MicroRNAs are small noncoding RNAs that associate with Argonaute (AGO) protein to form a silencing complex, which regulates a gene expression (Jonas and Izaurralde, 2015). MicroRNAs accomplish essential post-transcriptional regulatory step of gene expression regulation through either the degradation of a transcript or the inhibition of translation and are involved in key cellular processes, such as apoptosis, proliferation, or differentiation (He and Hannon, 2004). Human microRNA-mRNA Interactome of coding transcripts contain potential sites for microRNA regulation (Bartel, 2004; Friedman et al, 2009). Human genome encodes approximately 2,600 mature microRNAs (miRBase v.22) and, according to GENCODE data (v.29), more than 200,000 of transcripts, including isoforms with slight variations. The mapping of microRNA–mRNA interactions is far from being complete due to the recognized challenge of computational prediction of mRNA–microRNA interactions
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