Molecular mechanisms of RNA-based regulation
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.
Part A
Part B
is devoted to the development and optimization of new methods for the investigation of RNA properties and function. These novel tools will be applied to understand the role of specific structural elements and conformational dynamics to induce regulatory functions of RNA, from model systems to riboswitch RNA. The developed tools will also be applied to systems defined in Part B, encompassing important RNA-protein complexes (RNP).
investigates the multiple roles of RNA as regulatory constituent in important RNP complexes, with special emphasis on the core and auxiliary translational machineries. Regulatory function encompasses architectural, guiding and modifying functions, and also functions in non-conventional translation initiation and translation reprogramming.