Characterizing the role of protein deubiquitination in ribosome biogenesis

Abstract

Eukaryotic ribosome biogenesis requires hundreds of trans-acting factors and dozens of RNAs. Although most factors required for ribosome biogenesis have been identified, little is known about how they are regulated. Here, we reveal that the yeast deubiquitinating enzyme Ubp10 is predominantly localized to the nucleolus and ubp10 null cells have a significant reduction in pre-rRNAs, mature rRNAs, and translating ribosomes. Through proteomic analyses, we found that Ubp10 interacts with proteins that function in rRNA production and ribosome biogenesis. In particular, we discovered that the largest subunit of RNA polymerase I (RNAPI) is stabilized via Ubp10-mediated deubiquitination, and this is required to achieve optimal levels of ribosomes and cell growth. USP36, the human homolog of Ubp10, similarly regulates RNAPI in human cells and complements the ubp10 null allele for RNAPI stability and cell growth in yeast. Thus, stabilization of RNAPI through deubiquitination is conserved in eukaryotes. Additionally, we proposed other potential roles for Ubp10-mediated regulation in essential nucleolar functions. Our work now places Ubp10/USP36 as a key regulator of rRNA production.