Surprising discovery shows E. coli 2-thiouridylylase functions independently of iron-sulfur clusters
New research led by Professor Silke Leimkühler at the University of Potsdam has revealed new insights into how transfer RNA (tRNA) is modified in cells. E. coli (E. coli), focusing on a key enzyme called MnMA. Research results published in journal Inorganic matterchallenging previous beliefs about the role of iron-sulfur clusters in this process, showing that the MnMA enzyme only functions in the absence of these clusters. The discovery is an important step toward understanding the molecular processes behind tRNA modifications and helps explain why these processes differ across species.
The researchers explored how MnMA helps add sulfur to specific parts of tRNA, a process critical for the molecule to correctly translate genetic messages into proteins. Sulfur modifications at certain positions in tRNA ensure the correct matching of the genetic code and help maintain the stability of the molecule. Early research suggested that MnMA may rely on iron-sulfur clusters for this modification, but is this true? in E. coli Not sure. In other species, thermophilic archaea, similar enzymes require iron-sulfur clusters, but it is not certain whether this applies to E. coli MnMA enzyme.
Scientists conducted detailed experiments to clarify this. They purified MnMA from E. coli under aerobic and anaerobic conditions and tried adding iron-sulfur clusters to the enzyme. They found that although MnMA can bind to the iron-sulfur cluster, the cluster actually prevents the enzyme from functioning properly. The fact that MnMA works best without clusters clearly indicates that this enzyme does not require iron-sulfur clusters to function. E. coli. “Our research demonstrates that MnMA does not require iron-sulfur clusters to function. E. coli”, Professor Leimkühler emphasizes the importance of the findings.
The scientists also purified the MnMA enzyme with and without iron-sulfur clusters and tested its ability to add sulfur to tRNA under laboratory conditions. To do this, they used tRNA from a special strain of E. coli Iron-sulfur clusters cannot form alone. The results were clear: only MnMA enzymes without iron-sulfur clusters could perform sulfur transfer. The enzyme failed to work when the clusters were present, confirming that the clusters actually blocked the modification process.
The study also found that MnMA can only bind to tRNA of its own species, and this ability is not affected by whether it has iron-sulfur clusters. This species-specific behavior could explain why similar enzymes in other organisms require different conditions to function.
These researchers believe the findings have broader implications than just understanding how E. coli work. Modifications like the one studied are critical to the protein-making process. When something goes wrong with this process, it can lead to problems such as illness. In humans, for example, defects in similar pathways are associated with health conditions such as diabetes and certain mitochondrial diseases. This study helps clarify this conundrum by showing how tRNA modifications function in the absence of iron-sulfur clusters in bacteria, paving the way for further research to understand how these processes may differ in other species or under different environmental conditions. the way. In particular, oxygen sensitivity may provide a means of regulation to ensure that MnMA functions primarily under conditions of oxygen stress, when tRNA thiolation may be more important to ensure accurate decipherment of the genetic code, potentially providing an “oxygen switch” regulatory mechanism.
The team’s work showed that MnMA in E. coli works well without iron-sulfur clusters, which actually hinder its activity. This discovery helps resolve a debate in the scientific community and provides a clearer understanding of the molecular mechanisms behind bacterial tRNA modifications. These insights may guide future research into how similar processes function in other species and how these modifications affect larger biological processes involved in protein synthesis.
Journal reference
Ogunkola, M., Wolff, L., Fenteng, EA, Duffus, BR, & Leimkühler, S. (2024). “E. coli MnMA is a Fe-S cluster-independent 2-thiouridylylase. Inorganic matter12(3), 67.DOI:
