The synthesis of ribosomes is a complex but tightly regulated process in which the cell synthesizes equimolar amounts of four ribosomal RNAs in the nucleus, and of seventy-five ribosomal proteins in the cytoplasm, and assembles them into a ribosome in the nucleolus. We propose to study in Saccharomyces cerevisiae the mechanisms controlling both the transcription of ribosomal RNA and the synthesis of ribosomal proteins. Ribosomal RNA: We have identified a sequence in the rDNA repeat with many of the properties of an enhancer element. We plan to identify the precise sequences involved in this effect. We will ask whether this enhancer element: a) binds a specific transcription factor? b) is involved in the regulation of transcription of 35S prerRNA? c) is responsible for the 1:1 ratio of the transcription of 35S prerRNA and 5S RNA, whose gene lies between the enhancer and the 35S initiation site? Ribosomal Protein: The rates of transcription of most, if not all, ribosomal protein genes are tightly coupled. To understand the mechanism behind this coupling we will identify the sequences essential for the transcription of one ribosomal protein gene and then determine if similar sequences are used for other ribosomal protein genes. We will ask if the same sequences are involved in regulation of their transcription and/or whether there is a transcription factor specific for these genes. Finally, we will analyze the mechanism for translational control of ribosomal protein synthesis, with emphasis on testing the hypothesis that a regulatory molecule interacts with the m7G cap and its adjacent sequences.
| 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 |
| 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 |
| McIntosh, Kerri B; Warner, Jonathan R (2007) Yeast ribosomes: variety is the spice of life. Cell 131:450-1 |
| 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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