Karousis2

Validation of new human mRNA translation inhibitors derived from a cell-free translation screening

Validation of new human mRNA translation inhibitors derived from a cell-free translation screening

With support from the UniBern Forschungsstiftung, we acquired a luminescence plate reader, enabling the systematic optimisation and application of our human cell-free translation platform. This platform allows rapid, quantitative measurements of translation and has become a core technology in our laboratory.

Using this system, we performed a small-molecule screening that led to the identification of NT-2, a previously uncharacterised Fusarium-derived mycotoxin, as a potent and highly specific inhibitor of human ribosomes. Our study revealed an acute translation inhibition with a ribosome-preservation pathway not previously described for eukaryotic systems1.

Moreover, using the plate reader, we could obtain valuable data to assess the role of Coronaviruses in modulating human gene expression2 and to prepare lysates from different human cell types3,4.


For the acquisition of the plate reader, the UniBern Forschungsstiftung was acknowledged in the following publications from our group:

  1. Schwaller, N., Andenmatten, D., Luginbühl, J., Rabl, J., Chambon, M., Vesin, J., Turcatti, G., and Karousis, E.D. (2025). A human cell-free translation screen identifies the NT-2 mycotoxin as a ribosomal peptidyl transferase inhibitor. Preprint at bioRxiv, https://doi.org/10.1101/2025.10.11.680285
  2. Bäumlin, E., Andenmatten, D., Luginbühl, J., Lalou, A., Schwaller, N., and Karousis, E.D. (2025). The impact of Coronavirus Nsp1 on host mRNA degradation is independent of its role in translation inhibition. Cell Reports 44. https://doi.org/10.1016/j.celrep.2025.115488.
  3. Ziegelmüller, J., Kouvelas, N., Schwaller, N., Thambythurai, P., Hofer, A.M., Mühlemann, O., and Karousis, E.D. (2025). Efficient cell-free translation from diverse human cell types. Journal of Biological Chemistry 0. https://doi.org/10.1016/j.jbc.2025.110307.
  4. Schwaller, N., and Karousis, E.D. (2025). Protocol for monitoring mRNA translation and degradation in human cell-free lysates. STAR Protocols 6, 104073. https://doi.org/10.1016/j.xpro.2025.104073.

Evangelos Karousis, Ph.D.
Junior group leader
University of Bern – Dept of Chemistry, Biochemistry and Pharmaceutical Sciences
karousis.dcbp.unibe.ch

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