Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.
Open Access Thesis
Master of Science (M.S.)
Year Degree Awarded
Month Degree Awarded
A crucial step of the viral life cycle of Kaposi’s Sarcoma Herpesvirus (KSHV) lytic infection is the triggering of a massive RNA decay event termed “Host Shutoff”. Host Shutoff is driven by the viral endonuclease SOX which leads to the destruction of over 70% of the total transcriptome. This process cripples cellular gene expression and allows for viral reprograming of the cell for the purpose of viral replication. Co-evolution has led to the host developing a multitude of antiviral defenses aimed at preserving certain cellular RNAs linked to antiviral responses. One such defense are RNA secondary structures located within the 3’UTR of select host transcripts that protect them from SOX degradation. This structure, known as the SOX Resistant Element or SRE, has previously been isolated to a 200-nucleotide region found within the 3’UTR of the host transcript Interleukin-6. In this thesis, I sought to further define the structure of the IL-6 and other SREs using SHAPE-MaP to generate chemically-probed RNA structural models. Through this work, I demonstrated that the IL-6 SRE confers a form of active resistance to SOX cleavage, and based on structural analyses, likely acts as a scaffold for the recruitment of a protective ribonucleoprotein complex. This research highlights the importance of RNA secondary structures in influencing mRNA fate during viral infection and establishes the groundwork for understanding how these structural features can facilitate escape of cellular transcripts from viral endonucleases.
Miles, Jacob, "The SHAPE of U: Mapping Out Protective Elements in mRNA Escapees" (2020). Masters Theses. 977.