SPP 1784:  Chemical Biology of native Nucleic Acid Modifications

• Subject Area: Chemistry ; Biology ; Medicine
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255344185

The aim of this project is to unveil a hidden layer of information in the genetic code beyond the classical four-letter alphabet. While the sequence genetic code based on the four canonical Watson-Crick nucleosides has been an accepted paradigm for decades, an important aspect of it has recently been overturned. It became clear that additional nucleosides exist in DNA, which establish a second layer of information that is important e.g. to differentiation processes. Along the same line, we now start to understand that the numerous known modified RNA nucleosides are part of a similar “hidden” program that we are just beginning to understand. Indeed, deciphering the modified “genetic” code that is embodied by these modified DNA and RNA nucleosides is currently one of the hottest topics in (Chemical) Biology. In particular, the field of RNA modification is extremely visible, and even more active than at the beginning of the first grant period. This coordination proposal builds on significant achievements of the collective efforts during the first grant period. Outstanding publication records and conference activity have led to high international visibility. These aims will be further pursued during the second funding period, ensured by a bundle of measures including provisions for central network funds for analytical methods crucial to the field, in particular Deep Sequencing and LC-MS. The bundle further includes a coordination package to supply the coordinator with adequate infrastructure. A schedule for international conferences and workshops to ensure training of PhD students and co-workers will be continued. To make full use of all human resources, specific modules facilitate career starts for young scientists and young investigators and improve gender equity.

• DFG Programme: Priority Programmes
• International Connection: Switzerland

Projects

• Aminocarboxypropyl (acp) modified nucleotides in RNA: enzymes, structures and functions (Applicants Entian, Karl-Dieter ;  Wöhnert, Jens )
• Application of single-enzyme kinetics to investigate the turnover rate, processivity and specificity of DNA methyltransferase 1 (Applicant Jeltsch, Albert )
• Cellular imaging of RNA C-to-U editing (Applicants Meier, Jochen ;  Seitz, Oliver )
• Coordination Funds (Applicant Helm, Mark )
• Detection and functional characterization of queuosine and m5C modification in RNA (Applicants Ehrenhofer-Murray, Ann Elizabeth ;  Lyko, Frank )
• Detection and Identification of new RNA modifications (Applicant Helm, Mark )
• Discovery and characterization of RNA modifications in a bacterial model pathogen (Applicant Vogel, Jörg )
• Do chemical modifications of tRNAs contribute to the aggregation resilience of the highly Q-rich proteome in D. discoideum? (Applicant Hammann, Christian )
• Dynamics of methylated nucleosides and their derivatives in RNAs (Applicants Bohnsack, Markus T. ;  Höbartner, Claudia )
• Evolution of Chemical Modifications: from tRNAs to Transcriptome-Wide Surveys (Applicants Mörl, Mario ;  Stadler, Peter Florian )
• Fine-mapping of mRNA m6A sites in zebrafish development (Applicants Leidel, Sebastian ;  Rentmeister, Andrea )
• Functional and Structural Analysis of Eukaryotic snoRNP Complexes Catalysing rRNA Ribose Methylation (Applicants Carlomagno, Teresa ;  Entian, Karl-Dieter )
• Functional and Structural Analysis of the 18S rRNA aminocarboxypropyl transferase Bam1 (Applicants Entian, Karl-Dieter ;  Wöhnert, Jens )
• Identification and characterization of RNA modifications with immune-modulatory properties acting on Toll-like receptors (Applicants Dalpke, Alexander ;  Helm, Mark )
• Identification and characterization of small NAD-capped RNAs in yeast (Applicant Jäschke, Andres )
• Identification and functional characterization of pseudouridine in mRNAs and non-coding RNAs of the bacterial human pathogen Campylobacter jejuni (Applicant Sharma, Cynthia Mira )
• Investigation of RNA-specific base modification pathways (Applicant Meister, Gunter )
• Levels and functions of non-canonical nucleosides in messenger RNA (Applicant Carell, Thomas )
• Messenger RNA Modifications in Translation Regulation (Applicant Rodnina, Marina V. )
• Molecular mechanisms of m6A mRNA modification in Drosophila neurogenesis (Applicants Dieterich, Christoph ;  Roignant, Jean-Yves )
• Molecular mechanisms of Tet1 and Tet2 mediated DNA demethylation (Applicant Jurkowski, Tomasz )
• New DNA polymerases for the direct detection of epigenetic marks in RNA (Applicant Marx, Andreas )
• New tools for RNA modification dynamics analysis (Applicant Kaiser, Stefanie )
• Reprogramming genetic information at the RNA level: optimizing tools to address specific biological questions (Applicants Papavasiliou, Ph.D., F. Nina ;  Stafforst, Thorsten )
• Roles of tRNA modification cross-talk for mRNA decoding and translational fidelity (Applicant Schaffrath, Raffael )
• Structural and functional analysis of the tRNA-modifying enzymes DNMT2 and tRNA-guanine-transglycosylase (Applicant Ficner, Ralf )
• TALE-based Decoding of 5-Hydroxymethylcytosine by Selective Modification Response (Applicant Summerer, Daniel )
• The effect on translational efficiency of the i6A37 modification in cytoplasmic and mitochondrial tRNAs: Mitochondrial and selenoproteins. (Applicant Schweizer, Ulrich )

• Spokesperson: Professor Dr. Mark Helm