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Sass, S. ; Dietmann, S. ; Burk, U.C.* ; Brabletz, S.* ; Lutter, D. ; Kowarsch, A. ; Mayer, K.F.X. ; Brabletz, T.* ; Ruepp, A. ; Theis, F.J. ; Wang, Y.

MicroRNAs coordinately regulate protein complexes.

BMC Syst. Biol. 5:136 (2011)

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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.

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