The ribosome is responsible for protein synthesis and is essential in all cells. Its faithful translation of the genetic code and the proper regulation of its activity are necessary for normal cell growth and development. Ribosome assembly is a complex and dynamic process and mechanisms must exist that ensure the correct assembly of ribosomes in order to maintain the fidelity of translation. In addition, ribosome biogenesis accounts for a large portion of the energy expenditure of a rapidly dividing cell and must be coordinated with the metabolic needs of a cell. Indeed, cell proliferation in humans requires upregulation of ribosome biogenesis. Thus, understanding the mechanisms regulating ribosome biogenesis will provide insight for the development of new tools for controlling cell proliferation in disease states. The delineation of fundamental cellular pathways such as ribosome biogenesis and translation is also necessary for the intelligent development of new drugs that are specific to their intended cellular targets without impinging on other cellular pathways. We recently identified the nuclear export pathway for the large ribosomal subunit in yeast. We showed that its export depends on the export adapter protein Nmd3p and the export receptor Crm1 and that this export pathway is conserved in human cells. In this proposal, we will expand on these initial findings using reagents that we have developed in our studies of NmdSp. This proposal will: 1) Address how the export adapter and its receptor assemble on the large ribosomal subunit to mediate export. 2) Elucidate the events required to release the export adapter from the subunit after delivery to the cytoplasm. 3) Determine the function of Arx1 p and Reilp, two functionally related proteins that act at the polypeptide exit tunnel on the nascent large ribosomal subunit during export and as it enters the cytoplasmic pool of active subunits. ? ? ?
| 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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