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Title: Regulation of Interferon-Inducible 2’-5’-Oligoadenylate Synthetases by Adenovirus VAI RNA
Authors: Meng, Hui
Supervisor: McKenna, Sean (Chemistry)
Examining Committee: O'Neil, Joe (Chemistry) Khajehpour, Mazdak ( Chemistry) de Kievit, Teresa (Microbiology)
Graduation Date: February 2013
Keywords: Biochemistry
Structural biology
Innate immune response
Oligoadenylate synthetase
Viral double-stranded RNA
Issue Date: Oct-2012
Publisher: elsevier
Citation: Hui Meng, Soumya Deo, Shawn Xiong, Edis Dzananovic, Lynda J. Donald, Cody W. van Dijk, Sean A. McKenna, Regulation of the Interferon‐Inducible 2′–5′-Oligoadenylate Synthetases by Adenovirus VAI RNA, Journal of Molecular Biology, Volume 422, Issue 5, 5 October 2012, Pages 635-649, ISSN 0022-2836, 10.1016/j.jmb.2012.06.017.
Abstract: Viral double-stranded RNA is a key pathogen invasion signal recognized by the human innate immune system. All adenoviruses synthesize at least one highly structured RNA (VAI) to suppress this antiviral response by attenuating the activity of antiviral proteins. Surprisingly, VAI RNA was previously shown to positively regulate the activity of one interferon-inducible antiviral protein, 2’-5’-oligoadenylate synthetases (OAS). The present thesis focuses on investigating the regulation of a human OAS1 isoform by VAI RNA and its derivatives. An Escherichia coli protein expression and purification system has been developed for OAS1 protein production. A combination of biochemical and biophysical approaches was employed to examine VAI RNA binding affinity, activation potential for OAS1 and OAS1:VAI RNA complex formation. Taken together, I have found that while full-length VAI does indeed activate OAS1 in vitro, a truncated version lacking the terminal stem has the opposite effect, and this is the physiologically important response.
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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