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Open Access Highly Accessed Research article

MicroRNAs coordinately regulate protein complexes

Steffen Sass1, Sabine Dietmann12, Ulrike C Burk3, Simone Brabletz3, Dominik Lutter1, Andreas Kowarsch1, Klaus F Mayer1, Thomas Brabletz3, Andreas Ruepp1, Fabian J Theis1* and Yu Wang14*

Author Affiliations

1 MIPS, Institute for Bioinformatics and System Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany

2 Wellcome Trust Center for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

3 Department of Visceral Surgery, Universitätsklinikum Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany

4 Center for Life and Food Sciences Weihenstephan, Technicial University Munich, Emil-Ramann-Str. 4, D-85354 Freising, Germany

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BMC Systems Biology 2011, 5:136  doi:10.1186/1752-0509-5-136

Published: 25 August 2011

Abstract

Background

In animals, microRNAs (miRNAs) regulate the protein synthesis of their target messenger RNAs (mRNAs) by either translational repression or deadenylation. miRNAs are frequently found to be co-expressed in different tissues and cell types, while some form polycistronic clusters on genomes. Interactions between targets of co-expressed miRNAs (including miRNA clusters) have not yet been systematically investigated.

Results

Here we integrated information from predicted and experimentally verified miRNA targets to characterize protein complex networks regulated by human miRNAs. We found striking evidence that individual miRNAs or co-expressed miRNAs frequently target several components of protein complexes. We experimentally verified that the miR-141-200c cluster targets different components of the CtBP/ZEB complex, suggesting a potential orchestrated regulation in epithelial to mesenchymal transition.

Conclusions

Our findings indicate a coordinate posttranscriptional regulation of protein complexes by miRNAs. These provide a sound basis for designing experiments to study miRNA function at a systems level.