Structured RNAs Binding to Proteins Containing the dsRBD

描述(申请人提供)：双链RNA结合域(DsRBD)存在于所有生命王国中，特别是高等真核生物中。越来越多的证据表明，含有dsRBD的蛋白质，也就是。DsRBPs在基本的分子和细胞功能、感染和免疫以及发育中发挥着关键作用。DsRBP功能的一个关键共同主题是通过dsRBD与结构RNA配体结合。虽然完全双链dsRNA通常被用作体外结合伙伴，但最近的研究表明，内源性RNA配体的种类要多样化得多。然而，到目前为止，这些在体内具有生物学意义的RNA配体只被零星地和在小规模实验中进行了检查，导致数据不完整。在这项计划中，我们计划开发一些常用细胞系中dsRBDS/dsRBPs的RNA配体深度测序的实验方法，并通过计算探索它们的序列和结构特征以及生物网络。 与公共卫生相关：含有双链RNA结合域(DsRBD)的蛋白质，即dsRBPs，在正常和病理条件下都具有关键作用。它们功能的一个关键方面是与结构化RNA结合。人们对这些RNA伙伴知之甚少。通过使用深度测序技术和生物信息学，该项目将检查和编目与人类dsRBP家族成员相互作用的不同RNA物种种群。这些数据将有助于理解RNA-蛋白质的相互作用及其作用，将预测目前未知的dsRBP功能，并可能产生迄今未发现的RNA物种。

DESCRIPTION (provided by applicant): The double-stranded RNA binding domain (dsRBD) is present in all kingdoms of life, particularly in higher eukaryotes. Growing lines of evidence indicate that proteins containing dsRBDs, a.k.a. dsRBPs, play pivotal roles in essential molecular and cellular functions, infection and immunity, and development. A key common theme of dsRBP functions is binding to structured RNA ligands via dsRBDs. While perfectly duplexed dsRNAs are typically employed as binding partners in vitro, recent studies have indicated that endogenous RNA ligands are much more diverse. However, to date, these biologically relevant in vivo RNA ligands have been examined only sporadically and in small-scale experiments, resulting in fragmentary data. In this proposal, we plan to develop experimental methods for deep sequencing RNA ligands of dsRBDs/dsRBPs in a number of commonly used cell lines and to computationally explore their sequence and structure features and biological networks. PUBLIC HEALTH RELEVANCE: Proteins that contain the double-stranded RNA binding domain (dsRBD), known as dsRBPs, have pivotal roles in both normal and pathological conditions. A critical aspect of their functions is binding to structured RNAs. These RNA partners are poorly understood. By using deep sequencing technology and bioinformatics, this project will examine and catalog the distinct populations of RNA species interacting with members of the human dsRBP family. The data will help understand the RNA-protein interactions and their roles, will predict dsRBP functions that are presently unknown, and will probably yield hitherto undiscovered RNA species.