Unlocking Secrets of RNA: The Astonishing Structure of Ribozyme Unveiled

RNA molecules are essential components of the human organism: Within cells, they facilitate the transfer of genetic data and modulate gene activity. Some even serve as catalysts, enabling chemical reactions to occur at a pace that would otherwise be exceedingly slow or not happen at all. RNA-based enzymes are referred to as “ribozymes.”

A research group directed by Professor Claudia Höbartner at the University of Würzburg (JMU) has now unveiled the 3D structure of a highly unique ribozyme: SAMURI. This RNA molecule, synthesized in the laboratory, was first introduced by the team in 2023. The investigators from the Institute of Organic Chemistry successfully mapped the 3D configuration of SAMURI utilizing X-ray crystallography, in collaboration with Professor Hermann Schindelin from the Rudolf Virchow Centre in Würzburg.

Minor Adjustments with Significant Consequences

What renders SAMURI particularly intriguing for the scientists is its extraordinary capability: this ribozyme can chemically alter other RNA molecules at a precise location, subsequently affecting their functionality — for instance, either activating them or making them identifiable by proteins. Such alterations encompass crucial roles in nature and guarantee that RNAs function correctly. When mistakes occur in this regulation, such as an RNA experiencing an excess or deficiency of chemical modifications, it may result in the disruption of specific metabolic processes.

“We can liken RNA molecules to sentences formed from individual words and letters (nucleosides),” states Höbartner. “Even the slightest modifications at specific points — like changing a letter — can completely transform the meaning of a word or an entire sentence. Just as shifting the letter in ‘bat’ to ‘cat’ alters it to signify two distinct creatures with entirely different capabilities, a similar concept applies at the cellular level: ‘Here, the RNA assimilates new information through small chemical modifications made by nature. In scientific terminology, these are referred to as modifications. Enzymes perform chemical reactions on the RNA by employing a helper molecule known as S-adenosylmethionine, or SAM for short, vital for numerous cellular processes.’

SAMURI harnesses SAM to introduce alterations in the RNA. Intriguingly, some naturally occurring RNA molecules found in bacteria can also engage with SAM — yet without catalyzing the chemical reaction. These RNAs are referred to as riboswitches, and they do not chemically modify other RNAs.

With the decoded molecular structure of SAMURI, the researchers are now better equipped to address how the specific interactions of synthetic ribozymes with SAM diverge from those of natural riboswitches. “Research indicates that naturally occurring SAM-binding RNA may have evolved from early ribozymes that subsequently lost their catalytic function,” asserts Höbartner.

Foundational Research Informs the Advancement of New Therapeutic Approaches

Understanding the structure and functionality of catalytic RNA is vital for enhancing existing ribozymes and developing novel ones. For instance, research into natural RNA modifications is significant — both for visualizing them and for their application in therapeutic RNAs.

“Our discoveries could thus pave the way for new avenues in the formulation of RNA-based therapeutics,” comments Höbartner. “It is plausible that further optimized ribozymes may eventually serve as medicinal agents.”

This research was supported by the German Research Foundation (DFG).