SFB 902:  Molecular Principles 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.

DFG Programme Collaborative Research Centres

• A01 - Conformational dynamics of RNA regulation elements studied by NMR spectroscopy (Project Head Schwalbe, Harald )
• A02 - Development and characterization of engineered riboswitches (Project Head Süß, Beatrix )
• A03 - Structure and conformational flexibility of RNA studied by EPR spectroscopy (Project Head Prisner, Thomas F. )
• A04 - Synthesis of rigid spin labels and of other chemical tools to investigate RNA structure (Project Head Göbel, Michael )
• A05 - Dynamical Modelling of RNA-ligand complexes (Project Head Burghardt, Irene )
• A06 - Light-responsive riboswitches and miRNA activity (Project Head Heckel, Alexander )
• A07 - Molecular dynamics of RNA model systems studied by time-resolved optical and IR spectroscopy (Project Head Wachtveitl, Josef )
• A08 - Quantitative mapping of synaptic proteins and mRNA in neurons & a nano-analytical platform to probe binding mechanisms of RNA-binding proteins (Project Head Heilemann, Mike )
• A09 - Molecular Simulations of RNA Folding and Function (Project Head Hummer, Gerhard )
• A10 - RNA structure elucidation using site-specific dynamic nuclear polarization in the solid state (Project Head Corzilius, Björn )
• A11 - Regulating RNA by Cations - Insights from Molecular Simulations (Project Head Schwierz, Ph.D., Nadine )
• B01 - Regulation of mRNA in neurone (Project Head Schuman, Erin M. )
• B02 - Cell type-specific and stress-modulated microRNA target regulation (Project Head Dimmeler, Stefanie )
• B03 - Genome-wide analysis of RNA-recognition elements in African trypanosomes (Project Head Göringer, H. Ulrich )
• B04 - Non-conventional translation initiation in bacteria (Project Head Soppa, Jörg )
• B05 - Visualization of the RNA-Polymerase III Complete Transcription Cycle and the Bacterial Expressome by Cryo-Electron Tomography (Project Head Frangakis, Achilleas )
• B06 - Mechanism of recoding UGA for selenocystein insertion in Archaea (Project Head Rother, Michael )
• B07 - Control of mRNA translation and ribosome recycling by ABCE1 (Project Head Tampé, Robert )
• B08 - RNA elements required for pre-ribosome remodelling and pre-rRNA processing in 60S biogenesis in yeast (Project Head Bohnsack, Markus T. )
• B09 - The function of plant specific RNA and protein elements in ribosome biogenesis (Project Head Schleiff, Enrico )
• B10 - Structure and function of ribosome biogenesis factors and their functional complexes with small ribosomal subunit RNAs and RNPs (Project Head Wöhnert, Jens )
• B11 - New tools to study the dynamics of RNA and RNP distribution in neuronal cells (Project Heads Heckel, Alexander ;  Schuman, Erin M. )
• B12 - Structural dynamics of eukaryotic H/ACA complexes (Project Head Hengesbach, Martin )
• B13 - Dissecting the regulatory mechanisms of alternative polyadenylation and nuclear retention of mRNAs by SR proteins (Project Heads Müller-McNicoll, Michaela ;  Zarnack, Katharina )
• B14 - High-throughput identification of conserved structures in mRNAs (Project Head Weigand, Julia Erika )
• B15 - Identification of miRNA Targeting Hierarchies in Lymphocyte Development (Project Head Krueger, Andreas )
• B16 - Target cis elements of the RNA-binding protein Arid5a in inflammatory cytokine-based diseases (Project Head Schlundt, Andreas )
• B17 - Function, mechanism and structural basis for the regulation of gene expression by small regulatory RNAs (sRNAs) in γ-proteobacteria (Project Heads Bode, Helge Björn ;  Wöhnert, Jens )
• B18 - Structural Biology of SARS-CoV-2 by NMR spectroscopy (Covid19-NMR) (Project Head Schwalbe, Harald )
• MGK - Integrated Research Training Group (Project Heads Göringer, H. Ulrich ;  Müller-McNicoll, Michaela )
• Z - Central Tasks of the Collaborative Research Centre (Project Head Schwalbe, Harald )

Applicant Institution Goethe-Universität Frankfurt am Main

Participating University Technische Universität Darmstadt

Participating Institution Max-Planck-Institut für Biophysik; Max-Planck-Institut für Hirnforschung

Spokesperson Professor Dr. Harald Schwalbe