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Nucleic Acids Res. 2014 Jul;42(12):7539-52. doi: 10.1093/nar/gku465. Epub 2014 May 29.

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

Author information

1
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany ulf.schmitz@uni-rostock.de.
2
Laboratory of Systems Tumor Immunology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
3
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.
4
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa.
5
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany Department of Bioinformatics, CSIR-Indian Institute of Toxicology Research, 226001 Lucknow, Uttar Pradesh, India.

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/.

PMID:
24875477
PMCID:
PMC4081082
DOI:
10.1093/nar/gku465
[Indexed for MEDLINE]
Free PMC Article

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