New insights into the structure and reaction mechanism of a ribozyme
01/08/2025The crystal structure of the SAM-analog utilizing ribozyme SAMURI reveals a fascinating active site architecture and provides new insights into the evolution of catalytic RNAs and riboswitches.

Like proteins, RNAs are also able to fold into complex 3D structures and catalyze chemical reactions. Such RNA enzymes are then called ‘ribozymes’. In 2023, we reported an artificial ribozyme called SAMURI that site-specifically modifies a particular adenine nucleobase in a target RNA. It uses the natural metabolite S-adenosylmethionine (SAM) as a cofactor to transfer methyl or alkyl groups to the RNA of interest. In our most recent paper, which was published in Nature Chemical Biology, we now report the 3D structure of SAMURI obtained by X-ray crystallography. The structure provides important insights into the reaction mechanism of SAMURI and explains the high selectivity of the ribozyme for modifying a very specific target site. It also advances our understanding of natural 'riboswitches' – RNAs that recognize SAM but do not catalyze a reaction. Our results show that SAMURI and riboswitches interact with SAM in very different ways and make it possible to explain how ribozymes differ from riboswitches at the structural level. Our work suggest that riboswitches may represent evolutionary remnants of early ribozymes that lost their catalytic function over time.
Our new insights into the structure and function of SAMURI may help to further improve the catalytic activity of existing ribozymes. They may also aid the search for new catalysts capable of introducing other natural RNA modifications for which no ribozyme has yet been identified.