(from the application): This proposal is directed at understanding biogenesis of the large ribosomal subunit in yeast and its recruitment into translation. The ribosome is essential for the viability of all cells. In actively growing cells, ribosome biogenesis accounts for a large part of the energy expenditure of the cell and consequently ribosome biogenesis must be coordinated with the metabolic needs of a cell. Rapid cellular proliferation requires upregulation of ribosome biogenesis. Thus control of ribosome biogenesis is important for normal development. We identified Nmd3p, a conserved and essential protein in yeast, that is required for a late step in biogenesis of the large (60S) subunit. We have recently shown that Nmd3p forms a stable complex with 60S subunits and that this complex contains both nascent and mature subunits. Thus, Nmd3p is a protein that couples ribosome biogenesis and translation. In this proposal we will use genetic and biochemical techniques to determine the role of Nmd3p in subunit biogenesis as well as its role in translation. This work will involve the purification of nascent and mature free 60S ribosomal subunits and will provide the first physical characterization of these complexes. In addition to the analysis of Nmd3p we will test two models for the function of the protein complex composed of Ski2p, Ski3p and Ski8p. Mutations in the SKI genes result in elevated translation of poly(A)- mRNA and reduced 3'-degradation of mRNA. Two models accounting for these results are that this complex is required for normal 60S function or that this complex acts in a 3'-mRNA degradation pathway. Experiments will be carried out to distinguish between these two models.
| Hofman, Isabel J F; Patchett, Stephanie; van Duin, Mark et al. (2017) Low frequency mutations in ribosomal proteins RPL10 and RPL5 in multiple myeloma. Haematologica 102:e317-e320 |
| Ting, Ya-Han; Lu, Ting-Jun; Johnson, Arlen W et al. (2017) Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae. J Biol Chem 292:585-596 |
| Malyutin, Andrey G; Musalgaonkar, Sharmishtha; Patchett, Stephanie et al. (2017) Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis. EMBO J 36:854-868 |
| Pack, Chan-Gi; Inoue, Yuji; Higurashi, Takashi et al. (2017) Heterogeneous interaction network of yeast prions and remodeling factors detected in live cells. BMB Rep 50:478-483 |
| Hussmann, Jeffrey A; Patchett, Stephanie; Johnson, Arlen et al. (2015) Understanding Biases in Ribosome Profiling Experiments Reveals Signatures of Translation Dynamics in Yeast. PLoS Genet 11:e1005732 |
| Sardana, Richa; Liu, Xin; Granneman, Sander et al. (2015) The DEAH-box helicase Dhr1 dissociates U3 from the pre-rRNA to promote formation of the central pseudoknot. PLoS Biol 13:e1002083 |
| Sulima, Sergey O; Patchett, Stephanie; Advani, Vivek M et al. (2014) Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis. Proc Natl Acad Sci U S A 111:5640-5 |
| Sulima, Sergey O; Gülay, Suna P; Anjos, Margarida et al. (2014) Eukaryotic rpL10 drives ribosomal rotation. Nucleic Acids Res 42:2049-63 |
| Sardana, Richa; Zhu, Jieyi; Gill, Michael et al. (2014) Physical and functional interaction between the methyltransferase Bud23 and the essential DEAH-box RNA helicase Ecm16. Mol Cell Biol 34:2208-20 |
| Merwin, Jason R; Bogar, Lucien B; Poggi, Sarah B et al. (2014) Genetic analysis of the ribosome biogenesis factor Ltv1 of Saccharomyces cerevisiae. Genetics 198:1071-85 |
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