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

MiRNAs的调节活性受到其他miRNAs和RNA结合蛋白的存在的显著影响。考虑到miRNAs和限制性商业惯例之间的确切位置和关系类型(合作或拮抗)的定量方法目前正在开发中。目前大多数miRNA靶标预测方法只利用靶区附近的信息。缺点是缺乏对不同实验来源的整合，以及对问题的局部看法，没有考虑到完整的mRNA分子的全面表示。出于这些原因，我们将开发以下技术：1.通过迭代计算改进生成实验数据，为amiRNA介导的靶RNA切割和RNA-RNA结合蛋白质相互作用位点提供参数；2.以连贯和原则性的方式整合关注mRNA分子和miRNA-mRNA或RBP-mRNA相互作用各个方面的不同实验数据来源，例如：dsRNA-seq实验中的mRNA二级结构，CLIP-seq实验中的RBP结合，PAR-CL实验中的占位情况，3.使用对mRNA分子的全局视角进行工作。这将使我们能够深入了解基因表达的不同调控机制(RBPs，miRNAs)的相关作用，指导mRNA分子上的全球视角编码信息的设计。

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.