Research & Innovation
Publications
RiboScreen™ Technology Delivers Small-Molecule Ribodrugs to Convert Ribosomal Proteins into Molecular Valves for Tailored Protein Production Levels in Rare and Prevalent Disease
PMU Authors
Helmut Hintner, Bernadette Liemberger, Ulrich Koller, Johann W. Bauer
All Authors
Genevieve Edobor, Ronald Huber, Christoph Reiter, Hanna Gercke, Niklas Kaefer, Elli Kronsteiner, Bjoern Wimmer, Marlies Wimmer, Thomas Karl, Mark Rinnerthaler, Jan Krauss, Heinrich Krobath, Thomas Mohr, Christopher Gerner, Joerg von Hagen, Norbert Mueller, Helmut Hintner, Bernadette Liemberger, Ulrich Koller, Johann W. Bauer, Gazmend Temaj, Hannelore Breitenbach-Koller
Journal association
BIOMEDICINES
Abstract
Across all kingdoms of life, ribosomes are indispensable molecular machines that translate genetic information into the proteome of living cells. The fundamental catalytic centers of the ribosome, constructed primarily from ribosomal RNA (rRNA), exhibit remarkable conservation between the major domains of life. The ribosome's A-site deciphers the mRNA's triplet code, while the P-site synthesizes the growing protein chain and the E-site provides exit for deacylated tRNA; a distinct tunnel facilitates nascent polypeptide export. While the conservation of ribosomal proteins is less pronounced between bacteria and eukaryotes, striking homology exists from simple eukaryotes to humans. Ribosomal proteins were traditionally viewed mainly as scaffolding agents, steering rRNA folding during ribosome biogenesis and maintaining structural stability during translation. However, since the early 2000s, advances in structural and functional ribosome analysis have ushered in a more nuanced paradigm: ribosomes are no longer considered uniform machines. Instead, an array of rRNA and ribosomal protein modifications generates a spectrum of ribosome populations capable of specialized translation. RiboScreen (TM) technology leverages this regulatory potential of individual ribosomal proteins, enabling deliberate modulation of target protein output and representing a promising tool for correcting dysregulated protein expression involved in rare and common diseases. This review will first introduce relevant aspects of ribosome biology and then showcase the tools of this new technology. Finally, we report examples for the delivery of small molecules to target ribosomal proteins for tailored restoration of protein production levels in rare and prevalent diseases.
Keywords
RiboScreen (TM), Customized protein production, Novel drug targets, Precision intervention in rare and prevalent disease, Ribosomal proteins