dc.contributor.advisor | Lacy, Dana B | |
dc.contributor.advisor | Ren, Yi | |
dc.creator | Morris, Andrew Kennedy | |
dc.date.accessioned | 2020-09-22T22:18:26Z | |
dc.date.created | 2020-05 | |
dc.date.issued | 2020-05-19 | |
dc.date.submitted | May 2020 | |
dc.identifier.uri | http://hdl.handle.net/1803/16068 | |
dc.description.abstract | The nucleoprotein (NP) of the influenza A virus forms the structural packaging factor for the
viral genome by its binding to viral RNA as part of the viral ribonucleoprotein. It had been
previously shown that replication of the viral genome during infection requires the host DEADbox helicase UAP56, a critical factor in mRNA maturation and export, for facilitated recruitment
of NP to new viral ribonucleoproteins, but details of this were not well understood. In this
dissertation, we review mRNA export, and its integral part in influenza biology, and focus on
specifics of the NP UAP56 interaction. We demonstrate this interaction can be seen across viral
strains and NP oligomeric states. Novelly, we demonstrate that it is predominantly driven by the
N-terminal extension (NTE) of UAP56, while confirming existing reports of NP interaction with
the UAP56 RecA domains. Using crosslink mass spectrometry and mutagenesis, we demonstrate
that the UAP56 NTE binds by an electrostatic mechanism to the RNA binding cleft of NP, with
the center of the binding cleft being most critical for the interaction. We further demonstrate that
RNA competes with UAP56 NTE for NP binding. Our results provide a more complete
understanding of viral replication, and we conclude with a basic model and a speculative
discussion of remaining questions relating to the NP UAP56 interaction and the role of the larger
host mRNA export pathway as it relates to the virus in vivo. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.subject | Influenza, virology, mRNA export, TREX, UAP56, nucleoprotein, host-viral interaction, biophysics, biochemistry, viral replication | |
dc.title | Cellular mRNA Export Factor UAP56 Recognizes Nucleic Acid Binding Site of Influenza Virus NP Protein | |
dc.type | Thesis | |
dc.date.updated | 2020-09-22T22:18:26Z | |
dc.type.material | text | |
thesis.degree.name | PhD | |
thesis.degree.level | Doctoral | |
thesis.degree.discipline | Chemical & Physical Biology | |
thesis.degree.grantor | Vanderbilt University Graduate School | |
local.embargo.terms | 2022-05-01 | |
local.embargo.lift | 2022-05-01 | |
dc.creator.orcid | 0000-0002-4873-659X | |