The research focuses on the RNA modification m6A (N6-methyladenosine). It is one of the most common chemical modifications of messenger RNA – the molecules that form the link between our genetic information in the form of DNA and the world of proteins. Although it is known that m6A influences numerous biological processes, until now there has been insufficient understanding of how this modification affects the stability of RNA molecules and, consequently, gene activity in different cell types.
For their investigations, the research team used the flatworm Schmidtea mediterranea. This animal possesses an extraordinary ability to regenerate: even after severe injuries and amputations, it can completely regenerate lost body parts. As a result, this flatworm is regarded as an important model system for research into tissue regeneration from stem cells.
Using state-of-the-art direct RNA sequencing, the researchers succeeded in creating a high-resolution atlas of around 72,200 m6A marks across the flatworm’s entire transcriptome. They then investigated how these marks affect the lifespan of RNA molecules in different cell types. The results were surprising: the same chemical mark has different, and in some cases even opposing, functions depending on the cell type. While m6A stabilises certain RNA molecules in differentiated somatic cells, thereby prolonging their effect, in stem cells it promotes the degradation of m6A-marked RNA molecules. The researchers conclude that m6A acts as an additional level of control in gene regulation. It helps determine which genetic information remains available in a cell and which is rapidly removed. In this way, the RNA mark helps to maintain the identity of different cell types and ensure the balance between stem cells and specialised cells.
“Our findings show that the same RNA marker can perform very different functions in different cell types,” says Prof. Dr Claus-D. Kuhn, Professor of RNA Biochemistry at the University of Bayreuth’s Upper Franconia Medical Campus and last author of the study. “This provides new insights into the fundamental mechanisms by which cells establish and maintain their identity.”
The study was carried out by the two first authors, Constantin Höhn and Andreas Pittroff, from the RNA Biochemistry research group at the University of Bayreuth’s Upper Franconia Medical Campus. Their excellent work forms the foundation of the findings. They were supported by Prof. Dr. Lisa Hülsmann from the Bayreuth Centre of Ecology and Environmental Research (BayCEER). The work was also carried out in close collaboration with researchers from the IBMC (Institut de Biologie Moléculaire et Cellulaire) in Strasbourg.
