期刊
SCIENCE SIGNALING
卷 6, 期 289, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2004145
关键词
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资金
- European Molecular Biology Organization long-term fellowship
- Human Frontier Science Program long-term fellowship
- German Research Foundation (DFG) [GR 3823/1-1]
- Canadian Institutes of Health Research [MOP-97939, MOP-275194]
- National Sciences and Engineering Research Council
- Ontario Graduate Scholarship
- [RO1-GM067761]
- [R01-DK088718]
- [P01-CA120964]
- [RO1-GM045720]
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.
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