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The role of acute stress response in translation regulation

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Abstract

The post-transcriptional regulatory mechanisms cells mount in response to environmental stresses are varied and complex. Of particular interest is how cells regulate protein synthesis in response to severe stress as proteins are the ultimate, functional product of the ‘central dogma’ and protein synthesis represents a large energy burden. Research into translation during stress has traditionally focused on discrete aspects such as limiting initiation or altering RNA localization. In this dissertation, I attempt to employ a holistic approach to studying protein synthesis by considering translation machinery in the context of the general cytoplasm and by acknowledging the important role that RNA has in the process. To accomplish this, we provide an in-depth discussion of the reorganization of RNA and protein that takes place in stress-induced granules in Chapter 2. Next, using acute glucose starvation in yeast, we interrogate engagement of ribosomes with mRNAs and characterize how differential elongation influences gene expression in Chapter 3. Chapter 4 then discusses the results from an in vitro translation system I developed. With it, we found hallmarks of translation regulation observed during acute glucose starvation were maintained in cell extracts. Finally, Chapter 5 discusses possible future directions that can continue this work and includes closing remarks.

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This item is under embargo until December 20, 2023.