RNA binding proteins (RBPs) are vital enzymes for proper function of RNA regulatory pathways that range from chromatin packaging to mRNA translation. When RBPs and RNA interact, they form highly dynamic ribonucleoprotein (RNP) complexes, often in a combinatorial fashion. RNA-protein interactions are dependent on the RNA structure, which however is largely unreadable from the sequence content alone. Therefore, the binding and processing capacities of these protein partners remain poorly explored on the transcriptome-wide level. Some RBPs can become pathogenic when mutated. For example, TDP-43, DICER or TERC contribute to degenerative neurologic disorders, oncogenesis or premature ageing, respectively. Novel RNA-mediated disease mechanisms have emerged from these single candidate approaches. These studies have highlighted the importance of RBPs in transcriptome regulation and have contributed to our understanding of their roles in human disease phenotypes.
We are investigating the regulatory mechanisms of mammalian RBPs in noncoding and coding RNA processing by using an exhaustive and unbiased transcriptome-wide approach (RNA-sequencing and epigenetic profiling). In our study, we will interrogate the transcriptomes after perturbation of RBP function in human and mouse. Our long-term aim is to construct transcriptional networks governed by RBPs.