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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002197 |
| _version_ | 1811314473841983488 |
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| author | Lauren A. Richardson Benjamin J. Reed J. Michael Charette Emily F. Freed Eric K. Fredrickson Melissa N. Locke Susan J. Baserga Richard G. Gardner |
| author_facet | Lauren A. Richardson Benjamin J. Reed J. Michael Charette Emily F. Freed Eric K. Fredrickson Melissa N. Locke Susan J. Baserga Richard G. Gardner |
| author_sort | Lauren A. Richardson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:12:20Z |
| format | Article |
| id | doaj.art-7b94dcba6e8b47738fa43b79c1687adb |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T11:12:20Z |
| publishDate | 2012-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7b94dcba6e8b47738fa43b79c1687adb2022-12-22T02:49:05ZengElsevierCell Reports2211-12472012-08-012237238510.1016/j.celrep.2012.07.009A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I StabilityLauren A. Richardson0Benjamin J. Reed1J. Michael Charette2Emily F. Freed3Eric K. Fredrickson4Melissa N. Locke5Susan J. Baserga6Richard G. Gardner7Department of Pharmacology, University of Washington, Seattle, WA 98195, USADepartment of Pharmacology, University of Washington, Seattle, WA 98195, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USADepartment of Genetics, Yale University, New Haven, CT 06520, USADepartment of Pharmacology, University of Washington, Seattle, WA 98195, USADepartment of Pharmacology, University of Washington, Seattle, WA 98195, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USADepartment of Pharmacology, University of Washington, Seattle, WA 98195, USAEukaryotic 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.http://www.sciencedirect.com/science/article/pii/S2211124712002197 |
| spellingShingle | Lauren A. Richardson Benjamin J. Reed J. Michael Charette Emily F. Freed Eric K. Fredrickson Melissa N. Locke Susan J. Baserga Richard G. Gardner A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I Stability Cell Reports |
| title | A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I Stability |
| title_full | A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I Stability |
| title_fullStr | A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I Stability |
| title_full_unstemmed | A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I Stability |
| title_short | A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I Stability |
| title_sort | conserved deubiquitinating enzyme controls cell growth by regulating rna polymerase i stability |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712002197 |
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