GSBS Dissertations and Theses

Approval Date

3-5-2012

Document Type

Doctoral Dissertation

Department

Graduate School of Biomedical Sciences, Biochemistry and Molecular Pharmacology Program

Subjects

Dissertations, UMMS; RNA Stability; RNA, Ribosomal, 18S; Saccharomyces cerevisiae Proteins

Abstract

The molecular biology revolution of the 1960s has given rise to an enormous body of literature describing, in great detail, the inner workings of the cell. Over the course of the past 50 years, and countless hours at the bench, biologists have used the implications of basic research to produce vaccines, antibiotics, and other therapies that have improved both the quality and duration of our lives. Despite these incredible advances, basic questions remain unanswered. In even the simplest model organism, hundreds of essential genes have never been studied. Moreover, the central dogma of molecular biology—DNA to RNA to Protein—is understood largely in terms of how the cell functions under ideal conditions. What happens when things go wrong?

This study seeks to characterize one of the cell’s contingency plans—a quality control measure for the eukaryotic ribosome. Today, despite the abundance of ribosomes in all cells, we are only beginning to understand the details of how they function, and the mechanisms that monitor their behavior. Recently, inactivated ribosomes were shown to be destroyed by the cell's own quality control measures, potentially preventing them from harming the cell. This system, dubbed 18S Nonfunctional rRNA Decay, is known to utilize a pair of ribosome-binding proteins to carry out its function. Yet the pathway still functions, albeit more slowly, in the absence of these two proteins, suggesting that other components must exist. The work discussed here is largely concerned with identifying these other factors, characterizing their activities, and determining how the 18S Nonfunctional rRNA Decay pathway impacts the health of the cell.

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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