RNAmod - RNA Structures and the Epitranscriptome

About 150 bases for every million bases in our genome change their identity once they have been copied to messenger RNA. This process is called RNA editing. If editing takes place in genes encoding information for proteins, then the sequence of these proteins will be altered as well leading to slight difference in protein function. Editing is essential in humans and can lead to devastating diseases if altered or disturbed. In this project, I will take a closer look at the underlying mechanism of RNA editing and investigate a specific type, the so call A-to-I editing. In this process, an enzyme named ADAR only binds to its target region in the messenger RNA if this region is folded into a specific structure. In this project I will investigate these structures, the process by which they are formed and their evolutionary conservation. Starting from RNA editing I plan to extend my studies to other RNA modification which also alter the genetic code and the folding of the respective RNAs. I will search through genomes of vertebrates to identify the corresponding homologous positions of editing site known to exist in human and mouse and apply computer programs to predict RNA structures. The fascinating new part of this study is the analysis of the underlying processes of how these structures form and what alternative structure can be created such that other competing mechanisms are suppressed.

Background: About 150 bases for every million bases in our genome change their identity once they have been copied to messenger RNA. This process is called RNA editing. If editing takes place in genes encoding information for proteins, then the sequence of these proteins will be altered as well leading to slight difference in protein function. Editing is essential in humans and can lead to devastating diseases if altered or disturbed. RNA modification has been successfully used in the development of mRNA vaccines. Objective: In this project, we took a closer look at the underlying mechanism of RNA editing and investigated a specific type, the so call A-to-I editing. In this process, an enzyme named ADAR only binds to its target region in the messenger RNA if this region is folded into a specific structure. In this project we investigate these structures, the process by which they are formed and their evolutionary conservation. Starting from RNA editing we extended our studies to other RNA modification which also alter the genetic code and the folding of the respective RNAs. Results: By searching through genomes of vertebrates we identified evolutionary conserved RNA modification sites and identified RNA structures and sequence motifs that determine the modification sites. The fascinating new part of this study is the analysis of the underlying processes of how the cell decides which regions of the genetic code to post-transcriptionally alter. In collaboration with another research group we could show the impact of RNA modification in colitis and inflammation in a mouse model. https://doi.org/10.1101/2025.03.25.643676