An essential component of the human body are RNA molecules: They control gene activity and guarantee the transmission of genetic information within cells. Some even function as catalysts, enabling chemical reactions that would not otherwise occur or would occur very slowly. “Ribozymes” are enzymes composed of RNA.
Researchers at the University of Würburg (JMU), under the direction of Professor Claudia Höbartner, have recently discovered the three-dimensional structure of SAMURI, a particularly unique ribozyme. The team initially introduced this lab-generated RNA molecule in 2023. Using X-ray crystallography and in cooperation with Professor Hermann Schindelin of the Rudolf Virchow Centre in Würzburg, the researchers from the Institute of Organic Chemistry were able to ascertain the three-dimensional structure of SAMURI.
The unique ability of SAMURI to chemically alter other RNA molecules at a particular location and so affect their function for instance, activating them or making them recognizable by proteins—is what the researchers find so intriguing. These changes guarantee that RNAs can perform their functions correctly and have some extremely significant functions in nature. Certain metabolic processes may fail if there are mistakes in this control, i.e., if an RNA undergoes too many or too few chemical modifications.
We can think of RNA molecules as sentences made up of individual words and letters (nucleosides),
Here, the RNA receives the new information by nature making small chemical changes to it. In science, these are called modifications. Enzymes carry out a chemical reaction on the RNA, using a helper molecule called S-adenosylmethionine, or SAM for short, which is important for many processes in the cell.
Claudia Höbartner
Additionally, SAMURI introduces RNA alterations using SAM. The fact that certain naturally occurring RNA molecules found in bacteria can interact with SAM without catalyzing the chemical reaction is intriguing. These RNAs are known as riboswitches, and they don’t alter other RNAs chemically.
Thanks to the deciphered molecular structure of SAMURI, the researchers can now better answer the question of how the specific interaction of artificial ribozymes with SAM differ from natural riboswitches. Studies suggest that naturally occurring SAM-binding RNA could be derived from earlier ribozymes that lost their catalytic function during evolution.
Claudia Höbartner
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Enhancing current ribozymes and creating new ones requires an understanding of the structure and function of catalytic RNA. For instance, it would be crucial for both the visualization of natural RNA changes and their application in therapeutic RNAs.
Our findings could therefore provide new directions for the development of RNA-based therapeutics,
It is conceivable that further developed ribozymes could one day be used as drugs themselves.
Claudia Höbartner
Source: University od Würzburg – News
Journal Reference: Chen, Hsuan, et al. “Structure and Catalytic Activity of the SAM-utilizing Ribozyme SAMURI.” Nature Chemical Biology, 2025, pp. 1-10, DOI: https://doi.org/10.1038/s41589-024-01808-w.
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