Skip navigation
Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp012b88qg09b
Title: UNDERSTANDING THE ROLE OF RNASE L IN THE INNATE IMMUNE RESPONSE TO DOUBLE STRANDED RNA
Authors: CHITRAKAR, ALISHA
Advisors: KORENNYKH, ALEXEI
Contributors: Molecular Biology Department
Keywords: innate immunity
interferon
Rnase L
translation reprogramming
Subjects: Molecular biology
Issue Date: 2019
Publisher: Princeton, NJ : Princeton University
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.
URI: http://arks.princeton.edu/ark:/88435/dsp012b88qg09b
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu
Type of Material: Academic dissertations (Ph.D.)
Language: en
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.