MiRNA and RNA-binding proteins as integral part of cell communication:context-based target prediction and validation

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The regulatory activity of miRNAs is significantly affected by the presence of other miRNAs and RNA binding proteins. Quantitative methods that take the exact location and the type of relation (cooperative or antagonist) between miRNAs and RBPs into account are currently being developed. Most current approaches for miRNA target prediction exploit only information in the vicinity of target regions. Shortcomings are the lack of integration of diverse experimental sources, and local views of problems which do not take into account a comprehensive representation of the full mRNA molecule. For these reasons we will develop techniques that 1. generate experimental data by iterative computational improvement that provide parameters for amiRNA mediated target RNA cleavage and mRNA-RNA binding protein interaction sites, 2. integrate in a coherent and principled way the different experimental data sources that focus on various aspects of mRNA molecules and miRNA-mRNA or RBP-mRNA interactions, such as: secondary structure of mRNA from dsRNA-seq experiments, RBP binding from CLIP-seq experiments, occupancy profile from PAR-CL experiments, 3. work using a global perspective on the mRNA molecule. This will allow us to gain insight into the correlated action of different regulatory mechanisms (RBPs, miRNAs) of gene expression guiding the design of the information encoding for the global perspective on the mRNA molecule.