21. March 2025

Starting points for the control of protein synthesis Starting points for the control of protein synthesis

Bonn researchers develop a versatile toolbox for the characterization of IRESes in cells

The research field of "cellular IRESes" lay dormant for decades, as there was no uniform standard of reliable methods for the clear characterization of these starting points for the ribosome-mediated control of gene expression. Researchers at the University Hospital Bonn (UKB) and the University of Bonn, in collaboration with Stanford University in California (USA), have now developed a toolbox as a new gold standard for this field. They hope to discover strong IRES elements that are directly relevant for synthetic biology and for application in emerging mRNA therapeutics. The results of their work have been published in The EMBO Journal.

Starting points for the control of protein synthesis - (from left)
Starting points for the control of protein synthesis - (from left) - Philipp Koch, Martin Haimann, Saurabh Dey and Kathrin Leppek develop a versatile toolbox for the characterization of IRESes in cells. © Rolf Müller, UKBonn
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Only recently has the ribosome - one of the oldest molecular machines in evolutionary terms - been recognized as an active regulator of gene expression at the level of protein biosynthesis. This is an important process for the development and function of cells, in which genetic information is converted into proteins. The final step, in which the information encoded on the messenger RNA (mRNA) is transferred, is known as translation. The "Immunobiochemistry" research group led by Prof. Kathrin Leppek at the Institute of Clinical Chemistry and Clinical Pharmacology (IKCKP) at the UKB is investigating the control of translation using the direct interaction of the ribosome with mRNAs. "As the central translation machinery that is essential for all life, the ribosome and the factors associated with it, such as proteins or RNA structures, are the focus of our research interest," says Prof. Leppek, a member of the ImmunosSensation2 Cluster of Excellence at the University of Bonn. "There is increasing evidence that ribosome composition influences selective translation such that customized ribosomes preferentially bind and translate certain mRNAs."

Role of IRESes in gene expression
As an example of such structures, which play an important role in the initiation of translation and thus in the regulation of gene expression, the Bonn researchers have now investigated...

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The authors would like to thank the Flow Cytometry Core Facility of the Medical Faculty at the University of Bonn

Philipp Koch et al.: A versatile toolbox for determining IRES activity in cells and embryonic tissues; EMBO; DOI https://doi.org/10.1038/s44318-025-00404-5

Prof. Kathrin Leppek
Institute for Clinical Chemistry and Clinical Pharmacology
University Hospital Bonn
ImmunosSensation2, University of Bonn 
Phone: +49 (0)228/287-51158
E-Mail: kleppek@uni-bonn.de

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