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Sci Signal. 2013 Aug 20;6(289):ra70. doi: 10.1126/scisignal.2004145.

Conserved regulators of nucleolar size revealed by global phenotypic analyses.

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1
1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

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.

PMID:
23962978
PMCID:
PMC3964804
DOI:
10.1126/scisignal.2004145
[Indexed for MEDLINE]
Free PMC Article
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