Katja Petzold

Project summary

How does RNA move?

The way RNA molecules move matters, as Katja Petzold has shown. Her research group is the first to demonstrate that excited states in RNA molecules play a crucial role in their function. If it were possible to influence the movement of RNA molecules, this could create entirely new opportunities for regulating their function.

 

Only 25 per cent of the human genome codes for proteins, while the remainder was previously regarded as “junk”. It has now been discovered that 75 per cent of the genome codes for RNA, opening up a new world of RNA molecules with unknown functions. These RNA molecules move, and their movements regulate their function.

 

Until now, we have only been able to capture snapshots of RNA molecules. However, to understand how RNA movement determines function, we need to observe these molecules in motion. Imagine that we do not know what a pair of scissors is and that our only clues are pictures of closed scissors. It would be difficult to determine their function. Only when we see the scissors opening and closing does their function become apparent. The open scissors are analogous to an excited state of an RNA molecule. Using nuclear magnetic resonance (NMR), we are the first research group to demonstrate excited states in RNA and show that they are crucial to RNA function.

 

The aim is to use nuclear magnetic resonance to investigate movements and excited states in two RNA systems, microRNAs and ribosomes, which are associated with conditions including cancer and infections. As excited states can control processes involving regulatory RNA molecules, this reveals an entirely new level at which RNA activities can be modulated. These activities are important in all biological processes, from cell development to bacterial and viral infections. Conventional structural biology explains biological functions and develops drugs on the basis of static snapshots. Our findings show that molecular dynamics must also be taken into account in drug development.