Neumüller, R.A., Gross, T., Samsonova, A.A., Vinayagam, A., Buckner, M., Founk, K., Hu, Y., Sharifpoor, S., Rosebrock, A.P., Andrews, B., Winston, F., Perrimon, N. (2013). Conserved regulators of nucleolar size revealed by global phenotypic analyses.  Sci. Signal. 6(289): ra70.

FBrf0222552

Research paper

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.

PMC3964804 (PMC) (EuropePMC)