title: Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA segregation.
abstract: The conserved protein kinase Rio1 localizes to the cytoplasm and nucleus of eukaryotic cells. While the roles of Rio1 in the cytoplasm are well characterized, its nuclear function remains unknown. Here we show that nuclear Rio1 promotes rDNA array stability and segregation in Saccharomyces cerevisiae. During rDNA replication in S phase, Rio1 downregulates RNA polymerase I (PolI) and recruits the histone deacetylase Sir2. Both interventions ensure rDNA copy-number homeostasis and prevent the formation of extrachromosomal rDNA circles, which are linked to accelerated ageing in yeast. During anaphase, Rio1 downregulates PolI by targeting its subunit Rpa43, causing PolI to dissociate from the rDNA. By stimulating the processing of PolI-generated transcripts at the rDNA, Rio1 allows for rDNA condensation and segregation in late anaphase. These events finalize the genome transmission process. We identify Rio1 as an essential nucleolar housekeeper that integrates rDNA replication and segregation with ribosome biogenesis.
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Maria G
authors: 0000000345649519
authors: MG
authors: Iacovella
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Cristina
authors: C
authors: Golfieri
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Lucia F
authors: LF
authors: Massari
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Sara
authors: S
authors: Busnelli
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Cinzia
authors: C
authors: Pagliuca
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Marianna
authors: M
authors: Dal Maschio
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Valentina
authors: V
authors: Infantino
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Rosella
authors: R
authors: Visintin
authors: 1] The Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, Vienna 1030, Austria [2] The IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr-Gasse 3, Vienna 1030, Austria.
authors: Karl
authors: K
authors: Mechtler
authors: Lehrstuhl für Biochemie III, Universität Regensburg, Universitätsstraβe 31, 93053 Regensburg, Germany.
authors: Sébastien
authors: S
authors: Ferreira-Cerca
authors: Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, Milan 20139, Italy.
authors: Peter
authors: 0000000197725881
authors: P
authors: De Wulf
mesh_terms: D000705:Anaphase / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004275:DNA, Ribosomal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012318:RNA Polymerase I / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics*; D056565:Sirtuin 2 / Q000235:genetics*
chemical_list: D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C568560:Rpa43 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D017346:Protein Serine-Threonine Kinases; C462948:Rio1 protein, S cerevisiae; D012318:RNA Polymerase I; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2