SFB 902: Molecular Principles of RNA-based Regulation

SFB 902：基于 RNA 的调控的分子原理

• 批准号: 161793742
• 金额: --
• 依托单位: Goethe-Universität Frankfurt am Main
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/161793742?language=en
• 关键词: SFB; 902; Molecular; Principles; 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.

RNA分子在细胞功能调控中起着重要作用。超过90%的人类基因组被转录成非编码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节网络增加了相当多的复杂性、严格性和监视层。这些层包括转录、翻译、mRNA前剪接、mRNA衰变和mRNA转运的调控，所有这些方面在CRC902中都得到了成功的研究。CRC902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，以及超分辨率光谱和结构和化学生物学的方法，专门针对RNA。此外，我们已经确定了rna在细胞调控中发挥主要作用的关键生物学问题。我们可以确定核糖开关的配体识别模式，并描述全长转录和翻译核糖开关调控功能的分子机制。我们解决了中心细胞机制，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和蛋白质辅助因子在植物和古细菌核糖体生物发生中的相互作用。在生物信息学的帮助下，我们不断发现新的顺式作用RNA元件，并在CRC902中进行结构和功能研究。CRC902支持的一种重要方法是逆向工程RNA调节模块，将其中一些调节元件（适体、核糖开关、mirna）置于光照控制下，并应用光照触发在神经细胞、植物和心血管疾病和免疫系统发育相关的细胞中随意释放RNA。