RNA molecules play a key role in all cellular processes. Interestingly, RNA molecules in living cells contain more than the standard four nucleotides Adenosine, Guanosine, Uridine and Cytidine. Instead, they are heavily modified by a vast array of different modifications. The first RNA modification was discovered more than 50 years ago, and today we know more than 130 different types of RNA modifications, some of which are conserved in all domains of life.

In recent years, most of the modifying enzymes have been identified. However, little is known about the exact function of these modifications and how modification defects lead to the observed complex phenotypes. In particular, some RNA modification defects are linked to neurodegeneration in higher Eukaryotes including humans. It is crucial to understand, why this is the case.

In his analysis of the ubiquitin related modifier 1 (Urm1p) Sebastian Leidel has unraveled an unexpected function of Urm1p in modifying Uridine34 (U34) in a set of cytoplasmic tRNA by substituting 2-oxygen by 2-sulfur. This finding established Urm1p as the first example of an ubiquitin like protein that can perform both a function in RNA modification and protein conjugation. Thus, Urm1p provides a unique snapshot of the evolutionary branchpoint between ubiquitin like proteins and cellular sulfur-carriers.

In our laboratory we use the baker's yeast Saccharomyces cerevisiae as our main workhorse to characterize key functions of non-coding RNAs and their modification. However, we are also using more complex experimental systems to get insights into the function of RNA modification in the developing brain and in the context of disease. To this end we employ a large set of techniques from the fields of molecular biology, biochemistry, genetics and cell biology.

Our current key questions are:

  • What is the role of ncRNAs in cellular processes?
  • How is the function of ncRNAs influenced by RNA modifications?
  • How do RNA modifcation systems work and how are they regulated?
  • How do RNA modification defects give rise to degenerative phenotypes?
  • What are the mechanistic details of the URM1-pathway?

More about our research:

Research report 2016 "Protein folding – why speed matters" in the Yearbook of the Max Planck Society.

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