Unravelling the biological roles of self-cleaving ribozymes in bacteria

• Applicant: Dr. Christina E. Weinberg
• Subject Area: Biochemistry ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495144294

Ribonucleic acids (RNAs) fold into intricate structures and perform a variety of biological functions. Some structured RNAs, called ribozymes, dramatically accelerate chemical reactions. Although proteins are the dominant biological catalysts today, ribozymes are thought to have been much more abundant during a time in which life on Earth relied only on RNA as both catalyst and information carrier. In this “RNA World” era, many functionally diverse ribozymes would have performed all the chemistry required for life. Today, RNAs still catalyze essential cellular reactions in every living organism. For example, self-cleaving ribozymes cut their own phosphate backbone at a specific site to generate two RNA fragments. Ten structurally distinct classes of self-cleaving ribozymes are known that collectively show a broad distribution within all domains of life. Seven of these ten classes have numerous ribozyme examples in bacteria. However, despite their high abundance and broad distribution among bacterial species, we know, with a single exception, nothing about the biological roles of self-cleaving RNAs in bacteria. Here, I propose to investigate how self-cleaving RNAs shape life in bacteria by exploring ribozyme involvement in mRNA stability. Furthermore, we will study genes implicated in self-cleaving RNA function due to their high frequency near catalytic RNAs or due to their occurrence in conserved genomic loci. In our investigations, we will combine modern transcriptome analysis with classic genetic and molecular biology approaches to study ribozymes and their associated protein-coding genes. We will investigate ribozyme-protein interactions, test ribozymes implicated to rely on metabolite binding and use a novel RNA-seq-based method developed in our lab to monitor ribozyme activity under different growth conditions in vivo. These investigations bear the potential to reveal entirely new biology important for bacterial adaptation and survival in ever-changing surroundings. By deciphering the function of unknown proteins and the exact roles of RNA self-cleavage in bacteria, we will gain new insights into the diverse roles of RNAs. These investigations put the spotlight on modern RNA-based mechanisms that are rooted in a primordial era in which life on earth has its origins.

• DFG Programme: Research Grants