From yeast to mammals: The exploration of a conserved, intrinsically disordered deubiquitinase that regulates ribosomal RNA synthesis

Ribosomes are a key component of cell cycle regulation and protein production. Proper control of ribosome synthesis is necessary for normal cellular functioning. Improper regulation can lead to cell death or uncontrolled growth. RNA Polymerase I is responsible for synthesizing three of the four ribosomal components of the ribosome. While the upstream signaling pathways required for initiation RNA Polymerase I are well understood, very little is understood about what systems regulate RNA Polymerase I elongation. This thesis explores new roles for the post-translational modification ubiquitin in regulating RNA Polymerase I. First, it identifies how the conserved yeast deubiquitinase Ubp10 is involved in removing ubiquitin from Rpa190, a required catalytic subunit of RNA Polymerase I. It presents evidence that Ubp10 regulates the ubiquitination of Rpa190, and that ubiquitination is used to regulate degradation of chromatin bound Rpa190. Second, it highlights how Ubp10 uses intrinsic disorder to interact with the network of ribosome processing proteins. Ribosomal RNA recruits up to 200 different proteins, most of which are required for ribosome biosynthesis, and this work highlights how Ubp10 uses linear motifs within its intrinsic disorder to interact with them during ribosomal RNA transcription. Finally, this work demonstrates that both the function and intrinsic disorder of Ubp10 are conserved up to human deubiquitinase USP36. It shows that USP36 is able to functionally rescue ubp10Delta yeast and is capable of interacting with ribosomal processing proteins via conserved binding modules.