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

Schmitz, Ulf, Lai, Xin, Winter, Felix, Wolkenhauer, Olaf, Vera, Julio, and Gupta, Shailendra (2014) Cooperative gene regulation by microRNA pairs and their identification using a computational workflow. Nucleic Acids Research, 42 (12). pp. 7539-7552.

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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

Item ID: 69001
Item Type: Article (Research - C1)
ISSN: 1362-4962
Copyright Information: © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Date Deposited: 18 Dec 2023 03:28
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310201 Bioinformatic methods development @ 34%
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