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|dc.contributor.other||Molecular Biology Department||-|
|dc.description.abstract||Mammalian cells use two central strategies to fight against a pathogenic signature like dsRNA (double stranded RNA). They i) secrete interferons and ii) arrest global protein synthesis due to regulated RNA decay caused by the 2-5A-RNase L axis of innate immunity. We have used X-ray crystallography, recombinant protein engineering, biochemistry, RNA and cell biology to understand the role of RNase L in the innate immune response to self and non-self dsRNA. When cells are challenged with non-self dsRNA mimicking viral infections, interferon proteins bypass RNase L mediated global translation arrest. This work enabled by a nature inspired 2-5A biosensor reveals a fundamental mechanism by which 2-5A-RNase L axis reprograms host translation to prioritize synthesis of defense proteins. On the other hand, when self dsRNA accumulates in cells, RNase L program is activated without an interferon response. We determine the molecular basis for this paradoxical lack of interferon responses and reveal a fundamental mechanism that cells employ to maintain intracellular dsRNA load. To summarize, this thesis examines RNase L biology in the context of interferon signaling and offers new insights into its role as a sensor of self and non-self dsRNA.||-|
|dc.publisher||Princeton, NJ : Princeton University||-|
|dc.relation.isformatof||The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: <a href=http://catalog.princeton.edu> catalog.princeton.edu </a>||-|
|dc.title||UNDERSTANDING THE ROLE OF RNASE L IN THE INNATE IMMUNE RESPONSE TO DOUBLE STRANDED RNA||-|
|dc.type||Academic dissertations (Ph.D.)||-|
|Appears in Collections:||Molecular Biology|
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