Researchers at the University of Würzburg have revealed the three-dimensional structure of SAMURI, a laboratory-generated RNA molecule with unique catalytic properties. This ribozyme, first introduced in 2023, can chemically modify other RNA molecules at specific sites, potentially influencing their function.
Claudia Höbartner's team, in collaboration with Hermann Schindelin, used X-ray crystallography to determine SAMURI's structure. This discovery provides insights into how artificial ribozymes interact with S-adenosylmethionine (SAM), a helper molecule crucial for cellular processes.
Professor Höbartner, senior author of the study published in Nature Chemical Biology, explains the significance of RNA modifications: "We can think of RNA molecules as sentences made up of individual words and letters (nucleosides). The smallest changes at individual points, such as the replacement of a letter, can completely change the meaning of a word or the entire sentence.”
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SAMURI's ability to introduce modifications in RNA using SAM is particularly noteworthy. While some natural RNA molecules in bacteria can interact with SAM, they don't catalyze chemical reactions. These are known as riboswitches. The structural understanding of SAMURI helps differentiate between artificial ribozymes and natural riboswitches in their SAM interaction.
This research has potential implications for developing RNA-based therapeutics. Professor Höbartner suggests, "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."
The study of SAMURI's structure and function contributes to the broader understanding of catalytic RNA, which is crucial for improving existing ribozymes and creating new ones. This knowledge could be particularly valuable in researching natural RNA modifications and their potential therapeutic applications.