The overall goal of this proposal is to understand the transcript degradation pathway and its relationship to translational control, using the budding yeast S. cerevisiae as a model system. The focus is on the XRN1 gene, encoding the major 5'-3' exoribonuclease activity of yeast and believed to be the major catabolic enzyme in the late stages of the RNA turnover pathway. The investigator intends to identify other genes in the pathway by screening for mutations that are synthetically lethal with xrn alleles (Aim 1) and to characterize the mutants obtained (including the already known SKI2 gene) in RNA turnover and translation, in vivo (Aim 2) and in vitro (Aim 4).
Aim 3 is directed at targeted mutagenesis of XRN1 to analyze its functional domains and obtain dominant negative mutations. Many proteins involved in RNA turnover and translation control appear highly conserved among eukaryotes and are thought to help the cell respond to such challenges as pathogenic infection and oncogenesis.
| 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 |
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| 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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