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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00933

Comprehensive analysis of human microRNA-mRNA interactome

  • 1Laboratory of functional genome analysis, Moscow Institute of Physics and Technology, Russia
  • 2Laboratory of functional genomics, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics (RCMG), Russia
  • 3School of Systems Biology, George Mason University, United States
  • 4School of Biomedicine, Far Eastern Federal University, Russia

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.

Keywords: microRNA, regulation of gene expression, microRNA-mRNA interactions, microRNA binding sites, miRNA-target RNA duplexes, web tool for searching microRNA-binding regions

Received: 21 May 2019; Accepted: 05 Sep 2019.

Copyright: © 2019 Plotnikova, Baranova and Skoblov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD. Olga Plotnikova, Moscow Institute of Physics and Technology, Laboratory of functional genome analysis, Dolgoprudny, Russia, plotnikova@phystech.edu