"Characterizing the Dynamic Nature and Regulatory Mechanisms of the Tra" by Joshua Mark Denson

Date of Award:

5-2025

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Sean J. Johnson

Committee

Sean J. Johnson

Committee

Nicholas Dickenson

Committee

Ryan Jackson

Committee

Joan Hevel

Committee

Peter Shen

Abstract

In every living cell, RNA molecules play crucial roles in carrying genetic information and regulating various biological processes. To maintain the cell's health, it is essential to remove defective or unwanted RNA molecules through a process called RNA surveillance. This dissertation focuses on a key component of RNA surveillance in the cell's nucleus, known as the TRAMP (Trf4-Air2-Mtr4 Polyadenylation) complex. By combining biochemical, biophysical, and structural approaches, this research uncovers new insights into how the TRAMP complex assembles, regulates its activities, and interacts with RNA molecules. The findings reveal that the TRAMP complex undergoes dynamic changes in its shape when it binds to RNA and that specific parts of the complex are critical for controlling its functions. Additionally, we show that RNA molecules move back and forth between different parts of the complex depending on the length of the poly(A) tail located on the 3’ end of the molecule. Efforts to determine the three-dimensional structure of the TRAMP complex using advanced microscopy techniques are also described. This work enhances our understanding of how the TRAMP complex works to help maintain the quality of RNA molecules within the cell.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Wednesday, May 01, 2030

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