Author: Le Hoa Tan
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Category :
Languages : en
Pages :

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Author: Kristina Shostak
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Category :
Languages : en
Pages :

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Author: Daniel P. Stewart
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Category :
Languages : en
Pages : 312

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Author:
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ISBN:
Category :
Languages : en
Pages : 270

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In eukaryotes, mRNA decay pathways are important for cellular response to various physiological conditions and also function in co-translational quality control systems that target translationally aberrant mRNAs for degradation. My work on identification and characterization of novel components and pathways of mRNA degradation and quality control in Saccharomyces cerevisiae is summarized below. I have identified Edc3p as a novel protein important for mRNA decay. Deletion of Edc3p leads to a defect in mRNA decay in strains deficient in decapping enzymes and, in combination with a block to the 3' to 5' decay pathway, causes exaggerated growth defects and synthetic lethality. An Edc3p-GFP fusion protein localizes in processing bodies, which are specialized cytoplasmic foci containing decapping proteins. Together, these observations indicate that Edc3p directly interacts with the decapping complex to stimulate the mRNA decapping rate. Quality control during mRNA translation is critical for regulation of gene expression. My work shows that yeast mRNAs with defects in translation elongation, due to strong translational pauses, are recognized and targeted for degradation via an endonucleolytic cleavage in a novel process referred to as No-Go Decay (NGD). The cellular mRNA decay machinery degrades the 5' and 3' cleavage products produced by NGD. NGD is translation-dependent, occurs in a range of mRNAs and can be induced by a variety of elongation pauses. These results indicate NGD may occur at some rate inresponse to any stalled ribosome. I also show that two highly conserved proteins, Dom34p and Hbs1p, homologous to the eukaryotic release factors eRF1 and eRF3 respectively, are required for NGD. Further characterization of the No-Go decay pathway indicates that Dom34p function during NGD is conserved across species. Identification of RPS30, a small ribosomal protein as a trans-acting factor during NGD suggests that the ribosome may have a novel role during NGD. Other experiments indicate that the No-Go decay pathway may cross talk with the unfolded protein response pathway. The identification of No-Go decay as a novel quality control pathway during translation elongation supports the existence of a global cellular mechanism for maintenance of translational quality control.

Author: Felix Schirmaler
Publisher:
ISBN:
Category :
Languages : en
Pages : 238

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Author: KATHLEEN CORRADO
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Category :
Languages : en
Pages : 194

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the germinated spores display no obvious terminal phenotype.

Author: Elizabeth Chen
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Category :
Languages : en
Pages : 574

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Author: Krystal Annette Laframboise
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Category :
Languages : en
Pages : 0

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The identification of genome maintenance genes in Saccharomyces cerevisiae has been limited to loss-of-function screens that ignore the consequences of gene overexpression. Here, I assay expression of the DNA damage-inducible gene, RNR3, using reporter synthetic genetic array (R-SGA) methodology to identify genes that result in genome instability when overexpressed. I find 41 of ~5100 genes screened result in increased RNR3 expression, including known DNA repair genes, transcriptional regulators of RNR3, and a subset of genes exhibiting elevated levels of spontaneous DNA damage as determined by the presence of Rad52 foci. 61% of genes identified had no reported connection to genome stability when compared to previous overexpression studies, leaving 25 novel putative genome maintenance genes for follow-up. Finally, I show that induction of RNR3 in known genome instability mutants is not always dependent on the upstream checkpoint kinase Dun1, suggesting a non-canonical Dun1-independent pathway for RNR3 up-regulation following checkpoint activation.

Author: Vidya Balagopal
Publisher:
ISBN:
Category :
Languages : en
Pages : 198

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In eukaryotes, regulation of translation and decay of messenger RNA are critical for fine-tuned control of gene expression. An important point of control is the key transition where mRNAs exit translation and assemble into a non-translating mRNP state that can accumulate in cytoplasmic granules such as P bodies and/or Stress granules. In the budding yeastSaccharomyces cerevisiae, the activators of decapping Dhh1 and Pat1 appear to promote the exit of mRNAs from translation. In my work, summarized below, I describe a new regulator of translation repression and mRNA degradation, Stm1, and its novel mode of action. First, I identified Stm1 as a novel regulator of translation repression and mRNA decay. Stm1 shows several genetic interactions with Pat1 and Dhh1, in a manner consistent with Stm1 promoting the function of Dhh1. This suggests that Stm1 has a role to play in translation repression and/or activation of mRNA decay.stm1 & delta; strains are defective in the degradation of a subset of mRNAs that includeEDC1andCOX17. These results strongly argue that Stm1 is a novel addition to the mRNA degradation machinery. Second, I have shown that Stm1, a known ribosome-associated protein, can bind and stall 80S ribosomes to repress translation and promote decay. Stm1 is able to repress translation and stall an 80S complexin vitro. Several mutations were identified in the protein, which link thein vitrophenotype to its biological functionin vivo. The analysis of different steps in translation reveals Stm1 functions in a novel manner to inhibit translation after the formation of an 80S complex. Since most of the regulation of translation is thought to happen at the stage of initiation, this study reveals a novel mode of translation regulation. These results also provide a direct and mechanistic link between ribosome function, inhibition of translation and the degradation of messenger RNAs.

Author: Donna Christine Moreira
Publisher:
ISBN:
Category :
Languages : en
Pages : 108

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