title: Conserved regulators of nucleolar size revealed by global phenotypic analyses.
abstract: Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I-mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I-mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry-based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules.
authors: 1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors: Ralph A
authors: RA
authors: Neumüller
authors: Thomas
authors: T
authors: Gross
authors: Anastasia A
authors: AA
authors: Samsonova
authors: Arunachalam
authors: A
authors: Vinayagam
authors: Michael
authors: M
authors: Buckner
authors: Karen
authors: K
authors: Founk
authors: Yanhui
authors: Y
authors: Hu
authors: Sara
authors: S
authors: Sharifpoor
authors: Adam P
authors: AP
authors: Rosebrock
authors: Brenda
authors: B
authors: Andrews
authors: Fred
authors: F
authors: Winston
authors: Norbert
authors: N
authors: Perrimon
mesh_terms: D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal / Q000502:physiology; D020459:Genes, rRNA / Q000502:physiology; D006657:Histones / 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 / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004271:DNA, Fungal; D004275:DNA, Ribosomal; D006657:Histones; D012331:RNA, Fungal; D012335:RNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D012318:RNA Polymerase I
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