A conserved deubiquitinating enzyme controls cell growth by regulating RNA polymerase I stability.
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 their regulation. Here, we reveal that the yeast deubiquitinating enzyme Ubp10 is localized to the nucleolus and that ubp10Δ cells have reduced 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 that this is required in order to achieve optimal levels of ribosomes and cell growth. USP36, the human ortholog of Ubp10, complements the ubp10Δ allele for RNAPI stability, pre-rRNA processing, and cell growth in yeast, suggesting that deubiquitination of RNAPI may be conserved in eukaryotes. Our work implicates Ubp10/USP36 as a key regulator of rRNA production through control of RNAPI stability.
Department of Pharmacology, University of Washington, Seattle, 98195, USA.
Lauren A
LA
Richardson
Benjamin J
BJ
Reed
J Michael
JM
Charette
Emily F
EF
Freed
Eric K
EK
Fredrickson
Melissa N
MN
Locke
Susan J
SJ
Baserga
Richard G
RG
Gardner
D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability / Q000502:physiology; D005816:Genetic Complementation Test; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal / Q000096:biosynthesis* / Q000235:genetics; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
D009687:Nuclear Proteins; D012331:RNA, Fungal; D012335:RNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; C501066:USP36 protein, human; D012318:RNA Polymerase I; C403282:UBP10 protein, S cerevisiae; D043222:Ubiquitin Thiolesterase