The 2023 Nobel Prize in Physiology or Medicine has been awarded to Katalin Karikó and Drew Weissman for their breakthrough discoveries to use modified RNA for therapeutic treatments. Together with Herbert Tschochner, we have written a short comment to celebrate the occasion. We highlight the importance of the discoveries made by Katalin Karikó and Drew Weissman and how they have contributed to the development of RNA-based therapies. The comment can be accessed at Pflugers Archiv – European Journal of Physiology via this link.

RNA interactome studies suggested that numerous metabolic enzymes possess the ability to bind RNA. This has fueled the REM hypothesis that describes the regulatory interplay of RNAs, metabolic enzymes and metabolites. In a collaborative effort, a consortium comprising the Meister, Suess, and Rossbach labs and headed by the Babinger lab, has investigated RNA binding of select enzymes in E.coli using iCLIP, SELEX, MST, and EMSA experiments. This revealed specific RNA interaction of glutamate-5-kinase (ProB) and quinone oxidoreductase (QorA). It will be exciting to learn about the functional consequences and the biological importance of these protein RNA interactions. The open-access publication can be found here: weblink.

In a close collaboration with Monica Pichler from the lab of Thomas Mock at at he University of East Anglia, we could establish ribosome profiling for the Diatom Thalassiosira pseudonana. This unicellular organism belongs to an important group of eukaryotic microalgea that play a key role as primary producers in aquatic ecosystems, generating 20-50% of the oxygen on the planet each year, and comprising approx. half of the organic material found in the oceans. With ribosome profiling now available for diatoms, it can now be determined how changing environmental conditions such as acidification of the oceans or an increase in water temperature affect protein synthesis in the model organism T.pseudonana. Please find the open access publication at Current Protocols: weblink.

Our protocol for rapid ribosome profiling of small input samples has been published in Nucleic Acids Research. We demonstrate the outstanding performance of the newly developed sequencing library preparation workflow and its reproducibility with minute amounts of sample (0.1 pmol of RNA). We would like to thank our collaborators (Meister lab at the University of Regensburg, Leidel lab at the University of Bern & König lab at IMB Mainz) for their support! Please find the open access publication here: weblink.

We would like to thank The Company of Biologists for additional funding of the EMBO practical course on measuring translational dynamics by ribosome profiling to be held at the Advanced Training Centre at the European Molecular Biology Laboratory (EMBL) in Heidelberg from March 26th to April 1st.

Are you interested in establishing ribosome profiling in your lab to analyze cellular translation comprehensively and quantitatively?

Check out our novel and simplified protocol! The standardized workflow employs an extremely rapid sequencing library preparation protocol (12 hours) that relies on solid phase extraction of reaction intermediates, making it easy to implement in any standard laboratory. The protocol yields data of extremely high quality from minute amounts input material allowing the analysis of samples that were previously not easily amenable to this type of experimentation.

Access the preprint on bioRxiv here

If you are interested in practical training on how to perform the experiments, make sure to apply for a spot in the EMBO Practical Course on Measuring translational dynamics by ribosome profiling (March 26 – April 1 2023 at EMBL Heidelberg)

Our study of the activity of tha TRIM-NHL protein Mei-P26, a regulator of cell fate in Drosophila, has now been published at Life Science Alliance (doi 10.26508/lsa.202201418).

In a close collaboration with the labs of Sebastian Glatt (Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University Krakow, Poland) and Janusz Bujnicki (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw, Poland), we could solve the first high resolution structure of the Mei-P26 NHL domain and define a consensus RNA motif that it recognizes. Molecular dynamics simulations allowed us to predict and subsequently experimentally validate key amino acid residues involved specific RNA recognition, highlighting differences to other NHL domains. Using individual nucleotide resolution cross-linking and immunoprecipitation (iCLIP), we could identify RNA targets of Mei-P26 in cultured Drosophila cells and demonstrate the protein can either repress or activate its genuine mRNA targets. Regulation requires the NHL domain of the protein but is independent of its function as a ubiquitin ligase.

In particular, the last finding significantly expands our understanding of TRIM-NHL protein-mediated gene regulation. These proteins were previously considered to exclusively act as repressors of gene expression. Strikingly, Mei-P26 itself appears to lack any regulatory activity suggesting that the regulatory outcome is determined by the recruitment of different co-factors, some of which have previously been identified.

Pünktlich zum Weltkrebstag, dem 04. Februar, erscheint eine Pressemitteilung über unsere Forschungsergebnisse. Gemeinsam mit unseren Partnern Robert Ahrends, Grischa Tödt, Björn Tews und Christiane Knobbe-Thomsen, haben wir einen neuen Mechanismus entdeckt, der in Tumorzellen eine Resistenz gegen weit verbreitete Chemotherapeutika auslöst. Diese Chemoresistenz hat dramatische Folgen für betroffene Patienten, da die Behandlung stark eingeschränkt wird. Ein besseres Verständnis des Mechanismus der Chemoresistenz soll zukünftig neue Therapieoptionen ermöglichen.

Gefördert wurde die Forschungsarbeit im SUPR-G (Systems Biology of the Unfolded Protein Response in Glioma) Konsortium durch das Bundesministerium für Bildung und Forschung (BMBF) im Rahmen der e:med Initiative (Maßnahmen zur Etablierung der Systemmedizin).