Falsone, S Fabio, Meyer, N Helge, Schrank, Evelyne, Leitinger, Gerd, Pham, Chi LL, Fodero-Tavoletti, Michelle T, Holmberg, Mats, Dulle, Martin, Scicluna, Benjamin J, Gesslbauer, Bernd ORCID: 0000-0003-4910-8322, Rückert, Hanna-Marie, Wagner, Gabriel E ORCID: 0000-0002-5704-3955, Merle, David A, Nollen, Ellen A, Kungl, Andreas J, Hill, Andrew F ORCID: 0000-0001-5581-2354, Cappai, Roberto ORCID: 0000-0002-9505-8496 and Zangger, Klaus ORCID: 0000-0003-1682-1594 (2012) SERF protein is a direct modifier of amyloid fiber assembly. Cell Reports, 2 (2). pp. 358-371. ISSN 2211-1247

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 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.

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