Gerber:What We Do
RNA-binding proteins and posttranscriptional coordination of gene expression
Gene expression must be tightly controlled to ensure coordinated synthesis of the cells’ macromolecular components. Besides transcriptional control, it has become evident that also the later post-transcriptional steps – namely the processing, transport, turnover and translation of mRNAs – are pivotal for the diversification and spatiotemporal control of gene expression. Hundreds of RNA-binding proteins and non-coding RNAs mediate post-transcriptional control with widespread implications in cell physiology and disease. Nevertheless, the targets and functions for most RNA-binding proteins and non-coding RNAs are not known.
We have been combining genome-wide analysis with classical biochemical and genetic tools to identify the RNA targets of RNA-binding proteins and to investigate post-transcriptional gene regulation on a global scale. Importantly, these studies revealed that RNA-binding proteins bind to and coordinate groups of mRNAs that code for proteins, which are localized to the same subcellular compartment, act in the same pathway or are components of macromolecular complexes, forming so-called RNA regulons. Moreover, these set of RNAs often bear conserved sequence/ structural elements that likely represent binding sites for RNA-binding proteins. These findings suggested the presence of a highly-organized and elaborate post-transcriptional regulatory system that may affect virtually every mRNA in a cell.
We are further exploring the post-transcriptional regulatory landscape. On the one hand, we study specific RNA-binding proteins that coordinate the localization, decay or translation of mRNAs in the cytoplasm. Here, one current focus is given on recently discovered 'unconventional' RNA-binding proteins, such as metabolic enzymes; and we aim to understand functional implications of those RNA-enzyme interactions. We also work in the area of RNA-therapeutics aimed to better understand how RBPs critically control expression of therapeutic mRNAs; and we develop models studying autoregulatory feedback control of RNA-binding proteins. On the other hand, we characterize the translatome – which refers to all mRNAs that are associated with ribosomes for protein synthesis (Halbeisen et al. 2009) – and we currently monitor its contribution during ageing and sleep in the brain and under pathological conditions. We primarily use budding yeast as model to establish new techniques and to elucidate principles of post-transcriptional control, and we work with mammalian cells to unravel implications in disease.