New collaboration to investigate forms of RNA modification

Universität Mainz Institute of Pharmaceutical and Biomedical Sciences of Mainz University to collaborate with Monash University and ETH Zurich to investigate forms of RNA modification

Funded through the Human Frontier Science Program (HFSP), new avenues in RNA research are to be explored in a joint project involving Johannes Gutenberg University Mainz (JGU). The research will focus on RNA modifications caused by bacteria.

The cooperating partners aim to determine whether bacterial pathogens are capable of directly altering the RNA of their hosts with the help of so-called effector proteins. Participating in this innovative research project in addition to JGU are ETH Zurich and, as coordinator, Monash University in Melbourne, Australia.

The Human Frontier Science Program is geared to providing assistance to pioneering and unconventional research approaches the outcomes of which it is not possible to predict. We are particularly pleased that we and our partners have been so successful in meeting the exacting requirements of this demanding program."

Mark Helm, Professor and Head of Team, Institute of Pharmaceutical and Biomedical Sciences, Universitat Mainz

Project work will start in October 2023, supported with US$ 1.2 million in funding during its three-year duration.

Terra Incognita in the discipline of RNA research

Many of the bacteria that infect animals and plants release effector proteins into the cells of their hosts. These proteins compromise various physiological cellular processes, thus ensuring the continued viability of the bacteria.

It has already been demonstrated that bacterial effector proteins are capable of modifying the proteins of host cells by means of enzymatic intervention. However, the direct modification of RNA in eukaryotic cells, i.e., the cells of complex organisms with a clearly defined nucleus, has not been described to date. "We assume that certain proteins secreted by bacteria can alter host cells, and specifically the epitranscriptome, to ensure the better survival of the bacteria," added Professor Helm, describing the departure point of the research undertaking.

The researchers will first concentrate on Legionella, a bacterial species that causes lung inflammation disorders in humans, such as Legionnaires' disease. "We already know that Legionella bacteria release a whole range of different effectors that bind to the host RNA," said the biochemist. The aim is to find out how this process occurs, why the bacteria have chosen this particular method, and how exactly this benefits the Legionella themselves. The research team will thus be surveying as yet unexplored territory in host-pathogen research.

The interdisciplinary team consists of researchers working in the fields of microbiology, chemistry, and biophysics. Professor Elizabeth Hartland of Monash University will be acting as coordinator of the project entitled "Bacterial targeting of the host epitranscriptome". A specific Legionella effector protein, now designated LegC4, has already been discovered in her lab. The team of Professor Frédéric Allain of ETH Zurich will be contributing structural analysis of RNA protein complexes using state-of-the-art technology.

Targeting the epitranscriptome in the Mainz-based research group

As a result of its expertise in the field of RNA chemistry and the development of customized techniques, Professor Mark Helm's team at Mainz University will be involved in studying the epitranscriptome. The term itself denotes all the information contained in transcribed, processed, and modified RNA within cells.

The technological developments to be undertaken by the team will be driven by the need to decipher the various aspects of the epitranscriptome, particularly the numerous forms of RNA modifications. Helm is the speaker of CRC/Transregio 319 "RMaP: RNA Modification and Processing".

In addition, he is a principal investigator in the EMTHERA (Emerging Therapeutics) research cluster run by the Rhine-Main Universities (RMU), which is working to find new ways of treating infections, inflammation, and immune-mediated diseases. EMTHERA is one of the projects with which JGU is applying for a Cluster of Excellence in the upcoming competition of the German Excellence Strategy.

The prestigious Human Frontier Science Program promotes international collaboration in basic research focused on the elucidation of the sophisticated and complex mechanisms of living organisms. Following the initial launch of the program in 1989, 28 of the researchers that it has sponsored to date have won Nobel Prizes.