Cooperative gene regulation by microRNA pairs and their identification using a computational workflow

Ulf Schmitz, Xin Lai, Felix Winter, Olaf Wolkenhauer, Julio Vera, Shailendra K. Gupta

Research output: Contribution to journalArticleScientificpeer-review

63 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergize and which genes are target of cooperative miRNA regulation. In this paper, we present a computational workflow for the prediction and analysis of cooperating miRNAs and their mutual target genes, which we refer to as RNA triplexes. The workflow integrates methods of miRNA target prediction; triplex structure analysis; molecular dynamics simulations and mathematical modeling for a reliable prediction of functional RNA triplexes and target repression efficiency. In a case study we analyzed the human genome and identified several thousand targets of cooperative gene regulation. Our results suggest that miRNA cooperativity is a frequent mechanism for an enhanced target repression by pairs of miRNAs facilitating distinctive and fine-tuned target gene expression patterns. Human RNA triplexes predicted and characterized in this study are organized in a web resource at www.sbi.uni-rostock.de/triplexrna/.

Original languageEnglish
Pages (from-to)7539-7552
Number of pages14
JournalNucleic Acids Research
Volume42
Issue number12
DOIs
Publication statusPublished - 8 Jul 2014
Externally publishedYes
Publication typeA1 Journal article-refereed

ASJC Scopus subject areas

  • Genetics

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