title: MicroRNAs coordinately regulate protein complexes.
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.
authors.affiliation: MIPS, Institute for Bioinformatics and System Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Sass
authors.forename: Sabine
authors.initials: S
authors.lastname: Dietmann
authors.forename: Ulrike C
authors.initials: UC
authors.lastname: Burk
authors.forename: Simone
authors.initials: S
authors.lastname: Brabletz
authors.forename: Dominik
authors.initials: D
authors.lastname: Lutter
authors.forename: Andreas
authors.initials: A
authors.lastname: Kowarsch
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Mayer
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruepp
authors.forename: Fabian J
authors.initials: FJ
authors.lastname: Theis
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D035683:MicroRNAs / Q000502:physiology*; D046912:Multiprotein Complexes / Q000502:physiology*; D060066:Protein Interaction Maps / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D046912:Multiprotein Complexes; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein