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INVESTIGATING THE ESCAPE MECHANISM OF SRE BEARING MRNA TRANSCRIPTS DURING VIRAL HOST SHUTOFF

Abstract
During viral infection, the virus and host clash for control over gene expression in an evolutionarily arms race that has raged for thousands of years. During lytic replication, Kaposi's sarcoma associated herpesvirus (KSHV) triggers a massive RNA decay event known as host shut off. This causes over 70% of all RNA to be degraded suppressing the host antiviral response while freeing resources for viral replication. Our lab focuses on a subset of transcripts that escape from this viral degradation event using a cis acting 3' UTR element known as a 'SOX resistant element' or SRE. Although we have identified a couple of these transcripts and some of the proteins involved in their protection, the complete mechanism of protection from host shutoff has yet to be elucidated. In the first chapter, we used m6A-eCLIP to identify m6A modifications on SRE transcripts. We also characterized that this modification is necessary for SRE escape. In the second chapter we further characterized NCL/SRE densities during host shutoff through subcellular localization and mass spec and RNA sequencing. Finally in the third chapter we explored a method of SRE transcripts escaping from host shutoff induced nuclear retention of new transcripts through their interaction with a CRM-1 export pathway.
Type
dissertation
Date
2024
Publisher
Rights
License
http://creativecommons.org/licenses/by/4.0/