Researchers have unveiled the 3D configuration of an RNA enzyme named SAMURI. Their discoveries provide new perspectives on the development of ribozymes and the evolutionary origins of RNA that can catalyze chemical reactions.
A research team headed by chemist Claudia Höbartner has disclosed the three-dimensional structure of the RNA enzyme SAMURI. This research offers significant insights into the formation of ribozymes and traces the evolutionary path of catalytically active RNA.
RNA molecules are vital to the functioning of the human body. Within cells, they transmit genetic information and regulate gene expression. Some RNA types serve as catalysts, speeding up chemical reactions that might otherwise take much longer or not happen at all. These catalytic RNA molecules are known as “ribozymes.”
The research group, led by Professor Claudia Höbartner from the University of Würzburg (JMU), has successfully determined the three-dimensional structure of an intriguing ribozyme named SAMURI. SAMURI is a laboratory-created RNA molecule introduced by the team in 2023. They used X-ray crystallography in collaboration with Professor Hermann Schindelin from the Rudolf Virchow Centre in Würzburg to establish SAMURI’s 3D structure.
Minor Changes, Major Effects
SAMURI captures the attention of scientists due to its remarkable ability to chemically alter RNA molecules at designated sites, influencing their activity—such as activating them or making them recognizable to specific proteins. These modifications are crucial in nature, ensuring that RNAs function effectively. Any errors in this adjustment process—like an RNA strand having too many or too few modifications—can disrupt essential metabolic activities.
“We can visualize RNA molecules as sentences composed of individual words and letters (nucleosides),” Höbartner elaborates. “Even minor changes at select positions—like altering a letter—can completely change the meaning of a word or an entire sentence. Just as shifting ‘bat’ to ‘cat’ results in two very different animals with distinct capabilities, the same applies at the cellular level: RNA gains new information via small chemical alterations made by nature. Scientifically, we refer to these as modifications. Enzymes perform chemical reactions on RNA, using a helper molecule called S-adenosylmethionine, or SAM, which is essential for many cellular functions.”
SAMURI also uses SAM to change RNA. Interestingly, some natural RNA molecules in bacteria can bind to SAM but do not catalyze chemical reactions. These are termed riboswitches and do not modify other RNA strands.
With the detailed molecular structure of SAMURI now established, the researchers can investigate how artificial ribozymes interact with SAM compared to natural riboswitches. “Research suggests that naturally occurring RNA that binds to SAM may have evolved from earlier ribozymes that lost their catalytic functions over time,” Höbartner adds.
Fundamental Research Aids in Developing New Therapeutic Approaches
Comprehending the structure and role of catalytic RNA is essential for improving existing ribozymes and designing new ones. This knowledge will be particularly beneficial in studying natural RNA modifications, visualizing them, and applying them in therapeutic contexts.
“As a result, our findings could lead to new RNA-based therapeutic innovations,” says Höbartner. “It’s possible that more advanced ribozymes may eventually be used as actual medications.”
This study was funded by the German Research Foundation (DFG).
