Artificial Ribozyme SAMURI Offers Insights Into RNA Therapeutics

RNA molecules play vital roles in the human body by transferring genetic information and regulating gene activity. Some RNA molecules act as enzymes, called ribozymes, that facilitate essential chemical reactions. A notable ribozyme, SAMURI, has been analyzed by researchers at the University of Würzburg (JMU), who determined its three-dimensional structure through X-ray crystallography. This discovery sheds light on its ability to modify RNA molecules with precision.

The unique function of SAMURI

SAMURI stands out for its capacity to chemically alter specific RNA sites, enabling activation or recognition by proteins. This function is significant because RNA modifications are critical for proper cellular activity. Errors in these modifications can disrupt metabolic processes.

Using S-adenosylmethionine (SAM) as a helper molecule, SAMURI introduces chemical changes to RNA. Unlike riboswitches – naturally occurring RNAs that bind SAM but lack catalytic activity – SAMURI performs targeted modifications.

Insights from structural analysis

The study revealed how artificial ribozymes like SAMURI differ from natural riboswitches in their interaction with SAM. Researchers hypothesize that riboswitches may have evolved from ancient ribozymes that lost their catalytic abilities. The structural data not only clarify these differences but also provide a foundation for enhancing artificial ribozymes.

“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. Just as the word “bat” becomes “cat” by changing a letter, thus describing two distinct animals with very different abilities, it is similar at the cellular level:

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.”

Dr. Claudia Höbartner.

Implications for therapeutic development

This research contributes to understanding RNA modifications and could guide future therapeutic applications. Improved ribozymes might help visualize natural RNA modifications or act as therapeutic agents themselves. The findings also hold promise for developing RNA-based treatments for diseases associated with faulty RNA processing.

“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.”

Dr. Claudia Höbartner.

Reference: Chen HA, Okuda T, Lenz AK, Scheitl CPM, Schindelin H, Höbartner C. Structure and catalytic activity of the SAM-utilizing ribozyme SAMURI. Nat Chem Biol. 2025. doi: 10.1038/s41589-024-01808-w

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