Ubiquitin Signaling Regulates P-Body Assembly

Abstract

During the development of the central nervous system, neural stem cells give rise to different cell populations including neurons and glia. To en¬sure the genesis of the correct cell populations in the developing brain, there exists and intricate system of gene expression regulation. One such mechanism of gene expression regulation is the presence of membrane-less ribonucleoprotein (RNP) granules in the cell such as Processing bodies (PBs). These dynamic organelles are sites of RNA metabolism that can temporarily sequester mRNAs resulting in translational repression and/or decay. Therefore, to understand the molecular mechanism by which PBs regulate stem cell homeostasis, it is critical to delineate the signaling regulating PB dynamics. To this end, my thesis explores a novel non-proteolytic monoubiquitination-based signaling mechanism, where monoubiquitination of a core PB protein called 4E-T drives PB assembly. Mechanistically, PB dynamics are fine-tuned by a deubiquitinase called Otud4, which deubiquitinates 4E-T to disassemble PBs. This dynamic ubiquitination signaling therefore, functions as an essential molecular switch to coordinate PB dynamics in neural stem cells.