Characterizing the role of protein deubiquitination in ribosome biogenesis

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Characterizing the role of protein deubiquitination in ribosome biogenesis

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dc.contributor.advisor Gardner, Richard G en_US Richardson, Lauren Alexandria en_US 2012-08-10T17:38:27Z 2013-08-11T11:05:12Z 2012-08-10 2012 en_US
dc.identifier.other Richardson_washington_0250E_10107.pdf en_US
dc.description Thesis (Ph.D.)--University of Washington, 2012 en_US
dc.description.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. en_US
dc.format.mimetype application/pdf en_US
dc.language.iso en_US en_US
dc.subject ribosome biogenesis; RNA Polymerase I; ubiquitin en_US
dc.subject.other Cellular biology en_US
dc.subject.other Molecular biology en_US
dc.subject.other Pharmacology en_US
dc.title Characterizing the role of protein deubiquitination in ribosome biogenesis en_US
dc.type Thesis en_US
dc.embargo.terms Restrict to UW for 1 year -- then make Open Access en_US

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