Skip navigation
Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp012b88qg09b
Full metadata record
DC FieldValueLanguage
dc.contributor.advisorKORENNYKH, ALEXEI-
dc.contributor.authorCHITRAKAR, ALISHA-
dc.contributor.otherMolecular Biology Department-
dc.date.accessioned2020-07-13T02:01:27Z-
dc.date.issued2019-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/dsp012b88qg09b-
dc.description.abstractMammalian 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.language.isoen-
dc.publisherPrinceton, NJ : Princeton University-
dc.relation.isformatofThe 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.subjectinnate immunity-
dc.subjectinterferon-
dc.subjectRnase L-
dc.subjecttranslation reprogramming-
dc.subject.classificationMolecular biology-
dc.titleUNDERSTANDING THE ROLE OF RNASE L IN THE INNATE IMMUNE RESPONSE TO DOUBLE STRANDED RNA-
dc.typeAcademic dissertations (Ph.D.)-
pu.embargo.lift2021-10-04-
pu.embargo.terms2021-10-04-
Appears in Collections:Molecular Biology

Files in This Item:
This content is embargoed until 2021-10-04. For more information contact the Mudd Manuscript Library.


Items in Dataspace are protected by copyright, with all rights reserved, unless otherwise indicated.