Sass Steffen, Dietmann Sabine, Burk Ulrike C, Brabletz Simone, Lutter Dominik, Kowarsch Andreas, Mayer Klaus F, Brabletz Thomas, Ruepp Andreas, Theis Fabian J, Wang Yu
MIPS, Institute for Bioinformatics and System Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
BMC Syst Biol. 2011 Aug 25;5:136. doi: 10.1186/1752-0509-5-136.
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.
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.
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.
在动物中,微小RNA(miRNA)通过翻译抑制或去腺苷酸化来调节其靶信使RNA(mRNA)的蛋白质合成。miRNA经常在不同组织和细胞类型中共同表达,而有些则在基因组上形成多顺反子簇。共同表达的miRNA(包括miRNA簇)的靶标之间的相互作用尚未得到系统研究。
在此,我们整合了来自预测和实验验证的miRNA靶标的信息,以表征由人类miRNA调控的蛋白质复合物网络。我们发现了显著证据,表明单个miRNA或共同表达的miRNA经常靶向蛋白质复合物的多个组分。我们通过实验验证了miR-141-200c簇靶向CtBP/ZEB复合物的不同组分,提示在上皮-间质转化中存在潜在的协同调控。
我们的发现表明miRNA对蛋白质复合物存在协同的转录后调控。这些发现为在系统水平上设计研究miRNA功能的实验提供了坚实基础。