Many crucial processes in the cell are regulated at the level of the mRNA, and frequently such regulation involves other, non-coding RNA molecules. Therefore we study the molecular and structural details that govern the fate of RNA molecules in the cell. We use X-ray crystallography in combination with biochemical approaches and various assays both in vitro
and in vivo
One major topic is non-LTR retrotransposons and the molecular mechanisms underlying their propagation. These mobile genetic elements multiply via an RNA intermediate and can be regarded as molecular parasites. In the form of LINE-1 and Alu elements they massively amplified in the human genome, accounting for more than 25 % of its sequence. Their impact on human evolution and disease is just beginning to be analyzed in greater detail.
Another major topic is the regulation of mRNA turnover as a crucial element in the post-transcriptional regulation of gene expression. Together with Elisa Izaurralde we seek to understand the structural organization of the protein complexes that mediate mRNA 3’ deadenylation and mRNA 5’ decapping in eukaryotic cells. This includes the question how specialized mRNA decay pathways (such as the micro RNA pathway) converge at these central nodes of eukaryotic mRNA decay.
Finally, we also look into bacteria, where the Sm-like protein Hfq acts as central mediator in small RNA-based signaling and regulation. We investigate how Hfq specifically recognizes small RNAs despite their structural diversity and which conformational changes occur upon mRNA targeting.