SFB 902: Molecular Principles of RNA-based Regulation

RNA分子在调节细胞功能中起着重要作用。超过90%的人类基因组被转录成非编码RNA，这些RNA可以采用迷人的三维结构并发挥酶和调节功能。RNA为细胞和生物体中错综复杂的调控网络增加了相当多的复杂性、严格性和监视性。这些层次涉及转录、翻译、前mRNA剪接、mRNA降解、mRNA转运的调节-所有这些方面都在CRC 902中获得了巨大的成功。CRC 902的长期目标是研究RNA调节细胞功能的作用和潜力。我们开发了尖端的方法来研究RNA：光谱工具，包括NMR，EPR，IR和荧光光谱，理论描述，以及专门针对RNA的超分辨率光谱和结构与化学生物学方法。此外，我们已经确定了RNA在细胞调控中发挥重要作用的关键生物学问题。我们可以确定核糖开关中配体识别的模式，并描述全长转录和翻译核糖开关调控功能的分子机制。我们解决了中央细胞机器，RNA聚合酶和核糖体与循环因子的复合物的结构。我们研究了RNA和蛋白质辅因子在植物和古细菌核糖体生物合成中的相互作用。借助生物信息学，我们不断确定新的顺式作用RNA元件的结构和功能研究的CRC 902。CRC 902中支持的一种实质性方法是反向工程RNA调控模块，将这些调控元件（适体、核糖开关、miRNA）中的一些置于光控制下，并应用光触发剂在神经元细胞、植物和心血管疾病和免疫系统发育中暗示的细胞中随意释放RNA。

RNA molecules play important roles in the regulation of cellular function. More than 90% of the human genome is transcribed into non-coding RNA that can adopt fascinating three-dimensional structures and exert both enzymatic and regulatory function. RNA adds considerable layers of complexity, stringency and surveillance to the intricate regulation networks in cells and organisms. These layers involve regulation of transcription, translation, pre-mRNA splicing, mRNA decay, mRNA transport – aspects all of which are pursued in CRC902 with great success.It is the long-term goal of CRC902 to investigate the role and potential of RNA to regulate cellular function. We developed cutting-edge methodologies to study RNA: spectroscopic tools including NMR, EPR, IR and fluorescence spectroscopy, theoretical descriptions, and methods in super-resolution spectroscopy and Structural and Chemical Biology specifically geared towards RNA.Furthermore, we have identified key biological questions where RNAs play a major role in cellular regulation. We could determine the mode of ligand recognition in riboswitches and described the molecular mechanism of the regulatory function of full-length transcriptional and translational riboswitches. We solved structures of the central cellular machineries, RNA polymerases and complexes of ribosome with recycling factors. We investigate the interplay of RNA and protein cofactors in ribosome biogenesis in plants and archaea. Aided by bioinformatics, we continually identify new cis-acting RNA elements to be structurally and functionally investigated in the CRC902. A substantial approach supported within CRC902 is to inversely engineer RNA regulatory modules, put some of these regulatory elements (aptamers, riboswitches, miRNAs) under light control and apply light triggers to release RNAs at will in neuronal cells, in plants and in cells implied in cardio-vascular diseases and development of the immune system.