Posttranslational modifications (PTMs) are key signals modulating the function of eukaryotic proteins, for example by determining their sub-cellular localization. Arginine methylation is an abundant protein modification in eukaryotes, and distorted arginine modification levels are observed in common diseases like cancers and neurodegeneration. The major class of arginine-methylated proteins are RNA-binding proteins (RBPs).

This BioTechMed-Graz Flagship project aims at elucidation of the poorly understood molecular mechanisms by which arginine methylation regulates proteins through determining their sub-cellular localization. We joined our standing research interests and expertises in the fields of PTMs, nuclear import, and phase separation of RBPs, mutually opening up to systems biology, genetics and cell biology, structural biology and synthetic biology approaches. Together, we are studying the impact of arginine methylation on importin-cargo interactions, nuclear import, and formation of membrane-less organelles both in living cells and in vitro on a proteome, biochemical, biophysical and structural level. An improved understanding of PTM dependent signals determining sub-cellular targeting of RBPs will set the basis for pinning causal connections between dysregulated protein modification and disease.

The synergistic nature of this collaborative project is expected to result in a gain of scientific excellence and international recognition of BioTechMed-Graz, providing a fulcrum for the extension of our consortium to a larger ‘Dynamics of subcellular partitioning’ research focus in Graz.