Comprehensive Analysis of Human microRNA-mRNA Interactome.

TLDR: This study provides initial insight into the complexity of human microRNA–mRNA interactions and reveals 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.

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.