Investigating the dynamics of the neuronal RNP network

• Applicant: Professor Dr. Michael Kiebler
• Subject Area: Biochemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 506658941

RNA-binding proteins (RBPs) are thought to be major regulators of RNAs, controlling their cellular fate by assembly into ribonucleoproteinparticles (RNPs). RBPs thereby regulate virtually all steps of an RNA inside a cell, ranging from transcription, splicing, modification, intracellular localization, up to decay. Yet, we are only beginning to understand RNP assembly and how this might be regulated inside cells. In this proposal, we want to focus on the network of RBPs in primary neurons. Starting from the double-stranded RBP Staufen2 as a key RNA granule component, we would like to investigate how RNAs are packaged into RNPs. In particular, we would like to focus on direct as well as also compensatory effects in RNP composition caused by loss of Staufen2. A particular emphasis will thereby be given on other RNPs within the RNP network, e.g. Ago2, DDX6 and Pumilio2, all known interactors of Staufen2. Here, we will exploit a battery of interactor screens complemented with live-cell imaging and state-of-the-art biochemistry to unravel how the RBP network dynamically assembles and balances molecular and cellular alterations. Together, this will undoubtedly result in important new insight into the life cycle of RNPs and how the RBP network reacts to clinically relevant loss-of-function phenotypes in severe human neurodegenerative, neurological and neuropsychiatric diseases that are hallmarked by malfunctions of RNA granule components.

• DFG Programme: Research Grants