Folding of the FMN dependent riboswitch

黄素单核苷酸（FMN）核糖开关属于一类RNA分子，其感测代谢物的细胞浓度，并作为响应调节对代谢至关重要的基因的表达。代谢物结合域和核糖开关的表达平台之间的通信是动态的;对该过程的全面理解需要考虑时间敏感的参数。该项目分为两个部分：研究FMN核糖开关的折叠动力学（1）和鉴定诱导相同构象转变的合适FMN类似物（2）。核糖开关RNA的折叠将通过使用核碱基analgon 2-氨基嘌呤或特异性染料标记作为荧光报告物的荧光光谱法进行。此外，我们将使用各种新方法来监测RNA折叠的全局过程。在FMN还原时，代谢物改变其分子几何形状并从其结合位点释放。我们将使用这种配体形状控制策略来解决FMN核糖开关折叠是否完全可逆的问题。核糖开关是有吸引力的治疗靶点。我们将尝试识别与核糖开关结合并以与FMN相同的方式诱导构象转换的化合物，并在体外和体内研究其功效。

The flavine mononucleotide (FMN) riboswitch belongs to a class of RNA molecules that sense the cellular concentration of metabolites, and in response regulate expression of genes that are fundamental to metabolism. Communication between the metabolite binding domain and the expression platform of the riboswitch is dynamic; comprehensive understanding of this process requires consideration of time-sensitive parameters. The project is divided into two parts: studying the folding kinetics of the FMN riboswitch (1) and identifying suitable FMN analoga that induce the same conformational transition (2). Folding of the riboswitch RNA will be followed by fluorescence spectroscopy using the nucleobase analgon 2-aminopurine or specific dye labels as fluorescent reporter. Furthermore, we will use a variation of novel methods to monitor the global process of RNA folding. Upon reduction of FMN, the metabolite changes its molecular geometry and is released from its binding site. We will use this strategy of ligand shape control for addressing the question whether folding of the FMN riboswitch is fully reversible. Riboswitches are attractive therapeutic targets. We will try to identify compounds that bind to the riboswitch and induce conformational switching in the same manner as FMN and study their efficacy in vitro and in vivo.