An ischemic stroke is an extreme disturbance of the homeostasis of brain and body. Among other things, the immune system triggers an inflammatory reaction that can either overshoot or turn into an immune deficiency. For the first time, an international team of researchers – among them scientists from Goethe University Frankfurt, Germany – has now shown that tRNA fragments play a role in this immune reaction. Fragments of tRNAs, which transport amino acids during protein synthesis (“transfer RNA”), were long merely considered cellular waste. The aim of the research is to find new target structures for therapeutics.
Sebastian Lobentanzer of Goethe University, Frankfurt, has been studying small RNA dynamics in various contexts using bioinformatic methods. Recently, small RNAs have become more and more interesting for researchers, primarily because of their extensive regulatory functions. To examine these functions in stroke, Lobentanzer joined Katarzyna Winek of Hebrew University, Jerusalem, to study microRNAs and tRNA fragments in blood samples from ischemic stroke patients collected at Charité, Berlin. “tRNA fragments, which until now were only thought to be debris of the amino acid-transporting tRNAs, have recently been shown to possess biological functions; naturally, we were very interested in that,” explains the pharmacologist.
The project was initiated and led by Hermona Soreq (Hebrew University, Jerusalem, Israel) and Andreas Meisel (Charité, Berlin), who jointly study the contributions of small RNA regulators of cholinergic signaling in blood cells of stroke patients, funded by the Einstein Foundation. Katarzyna Winek from The Edmond and Lily Safra Center of Brain Science at The Hebrew University collaborated with Sebastian Lobentanzer at the Institute for Pharmacology and Clinical Pharmacy (AK Jochen Klein) at Goethe University Frankfurt, Germany.
This collaborative effort was able to show, for the first time, the involvement of monocytic tRNA fragments in the poststroke immune response. “Simply put, there may be a ‘changing of the guards,’ in which tRNA fragments replace microRNAs in monocytes,” explains Lobentanzer. “Bioinformatic network analyses show that these two small RNA species have vastly different functional roles in the immune response, and thus may work in synergy in the regulation of homeostasis.” In the long run, the researchers want to find therapeutics to modify these processes. Indeed, if the immune status of each patient after a stroke could be individually determined, many complications could be avoided.
Publication: Katarzyna Winek, Sebastian Lobentanzer, Bettina Nadorp, Serafima Dubnov, Claudia Dames, Sandra Jagdmann, Gilli Moshitzky, Benjamin Hotter, Christian Meisel, David S Greenberg, Sagiv Shifman, Jochen Klein, Shani Shenhar-Tsarfaty, Andreas Meisel, Hermona Soreq: Transfer RNA fragments replace microRNA regulators of the cholinergic post-stroke immune blockade. PNAS https://doi.org/10.1073/pnas.2013542117