Post-transcriptional regulation is highly versatile and adaptable in exploiting cellular time and space. RNA-binding proteins play a key role in the regulation of spatial and temporal changes in protein synthesis through control of transport, translation and decay of mRNA. Deregulation and failed coordination of these mechanisms contribute to the pathophysiological development and conditions.
Transcriptome-wide high-resolution maps of RNA-protein contacts allow us to study how these interactions control mRNA fate [Hafner & Landthaler et al., Cell 2010; Rybak-Wolf et al., Cell 2014]. Different next generation sequencing approaches are being applied to examine the function of RNA-binding proteins in mRNA biogenesis, translation and decay [Murakawa et al. Nature Communications 2015].
In addition, we have developed a UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics. We use this method to monitor dynamic changes of the mRNA-protein interactome to capture differentially binding proteins as a consequence of intra- and extra-cellular signals. [Milek et al., Genome Research 2017].
Our main interest is the understanding of post-transcriptional regulatory networks that control gene expression. Post-transcriptional regulation is highly versatile and adaptable in exploiting cellular time and space. microRNAs and RNA-binding proteins play a key role in the regulation of spatial and temporal changes in protein synthesis through control of mRNA transport, storage and translation. Deregulation and failed coordination of these mechanisms contribute to the pathophysiological development and conditions. A prerequisite for a systems level understanding of post-transcriptional regulation is a transcriptome-wide high-resolution map of RNA-protein contacts that allows us to study how these interactions control the fate of mRNAs.
We are using a novel crosslinking-immunoprecipitation approach (PAR-CLIP) in combination with “deep-sequencing” to identify functional RNA-protein interactions at a nucleotide resolution (Hafner & Landthaler et al.  Cell, 141). By using these RNA-protein interaction maps and combining them with cell-based and biochemical assays, we are aiming to understand the coordinated and combinatorial assembly of microRNAs, RNA-binding proteins and helicases on their target mRNAs as well as the structures and mechanisms guiding mRNA maturation, localization, turnover and protein synthesis in response to stress and environmental signals.