Date of Award

8-2009

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Physics

Committee Chair/Advisor

Spano, Meredith N

Committee Member

Alexov , Emil

Committee Member

Ke , Pu Chun

Abstract

The human ribosome is an RNA-protein complex responsible for protein synthesis in the cell. Crystal structures of bacterial ribosomes solved to date depict no protein sidechains within the catalytic core, or peptidyl transferase center (PTC). This region of the human ribosome comprises approximately 230 highly conserved nucleotides. Notably, several of the uridine bases clustered within the human PTC are post-transcriptionally modified to pseudouridines, as compared with bacterial analogues. Pseudouridines are base-rotated uridines, linked to their sugar moieties through C5-C1' linkages, affording additional hydrogen-bond donor groups at the N1 position of their rings. A connection was recently made between the absence of pseudouridines within the PTC and diseases such as dyskeratosis congenita, leukemia, and solid tumor cancers; however, the function of pseudouridine in the PTC is unknown. PTC RNA constructs are being synthesized with and without wild-type pseudouridine modifications to assess possible structural and dynamic roles of these bases. UV thermal denaturation and circular dichroism experiments are planned to identify key physical differences between the modified and unmodified PTC. Small angle x-ray scattering studies will also be performed on the two models for low resolution conformational comparison. Our goal is to make a significant contribution to the growing body of knowledge addressing the relationship between the absence of pseudouridines and malignancy.

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