The synthesis of ribosomes is a complex but tightly regulated process in which the cell synthesizes equimolar amounts of the four ribosomal RNAs in the nucleus, and of seventy-five ribosomal proteins in the cytoplasm, and assembles them into a ribosome in the nucleolus. The regulation of the synthesis of ribosomes is a key aspect of the regulation of growth in essentially all organisms. This proposal will use a largely genetic approach to study the mechanisms responsible for such regulation in Saccharomyces cerevisiae, with the aim of elucidating general regulatory mechanisms, and of understanding how cells can coordinate the expression of a large number of genes. We will examine the regulation of synthesis of ribosomal RNA with regard to hypotheses on the role of the enhancer element in the structural arrangement of the tandem rRNA genes, and with regard to the possibility of a regulatory mechanism acting through the transcribed spacer region. We will explore the coordinate regulation of the transcription of more than 100 ribosomal protein genes by identifying mutants that have lost either positive or negative control function. Such mutants will then be examined to provide insights into the mechanisms behind the coordinate regulation. S. cerevisiae has a number of abundant DNA binding proteins of apparently diverse function. One such protein, termed REB1, binds to the rDNA transcriptional control regions and elsewhere. Having identified and purified REB1, and cloned and sequenced its gene, we now will explore its function by analysis of the phenotypes of temperature sensitive mutants in REB1 and their suppressors. We expect to learn not only how such a protein functions but also what other components of the cell may interact with it. REB1 appears to share an unusual DNA binding domain with the oncogene, myb. By targeted mutation of the yeast protein we expect to learn more about the characteristics of such DNA-protein interactions.
| Gupta, Varun; Warner, Jonathan R (2014) Ribosome-omics of the human ribosome. RNA 20:1004-13 |
| Lee, Jaehoon; Moir, Robyn D; McIntosh, Kerri B et al. (2012) TOR signaling regulates ribosome and tRNA synthesis via LAMMER/Clk and GSK-3 family kinases. Mol Cell 45:836-43 |
| McIntosh, Kerri B; Bhattacharya, Arpita; Willis, Ian M et al. (2011) Eukaryotic cells producing ribosomes deficient in Rpl1 are hypersensitive to defects in the ubiquitin-proteasome system. PLoS One 6:e23579 |
| Warner, Jonathan R (2011) 18S rRNA: a tale of the tail. J Mol Biol 405:1-2 |
| Bhattacharya, Arpita; McIntosh, Kerri B; Willis, Ian M et al. (2010) Why Dom34 stimulates growth of cells with defects of 40S ribosomal subunit biosynthesis. Mol Cell Biol 30:5562-71 |
| Warner, Jonathan R; McIntosh, Kerri B (2009) How common are extraribosomal functions of ribosomal proteins? Mol Cell 34:3-11 |
| Bhattacharya, Arpita; Warner, Jonathan R (2008) Tbf1 or not Tbf1? Mol Cell 29:537-8 |
| McIntosh, Kerri B; Warner, Jonathan R (2007) Yeast ribosomes: variety is the spice of life. Cell 131:450-1 |
| Rudra, Dipayan; Mallick, Jaideep; Zhao, Yu et al. (2007) Potential interface between ribosomal protein production and pre-rRNA processing. Mol Cell Biol 27:4815-24 |
| Zhao, Yu; McIntosh, Kerri B; Rudra, Dipayan et al. (2006) Fine-structure analysis of ribosomal protein gene transcription. Mol Cell Biol 26:4853-62 |
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