Matching Items (937)
Filtering by
- Creators: Novak, Gail (Pianist)
Description
The splicing of precursor messenger RNAs (pre-mRNAs) plays an essential role in dictating the mature mRNA profiles of eukaryotic cells. Mis-regulation of splicing, due to mutations in pre-mRNAs or in components of the splicing machinery, is associated with many diseases. Therefore, knowledge of pre-mRNA splicing mechanisms is required to understand gene expression regulation during states of homeostasis and disease, and for the development of therapeutic interventions.Splicing is catalyzed by the spliceosome, a dynamic and protein-rich ribozyme composed of five small nuclear ribonucleoproteins (snRNPs) and ~170 auxiliary factors. Early interactions that occur in prespliceosomal complexes formed by the 5′- and 3′-splice-site bound U1 and U2 snRNPs are responsible for committing introns for removal. However, the mechanisms underlying these early interactions remain to be fully characterized for understanding the influence of alternative splicing factors and the impact of recurrent disease-associated mutations in prespliceosomal proteins. The goal of my dissertation research was to delineate the role of the U1 small nuclear RNA (snRNA) during prespliceosome assembly. By applying a cellular minigene reporter assay and a variety of in vitro techniques including cell-free protein expression, UV-crosslinking, electrophoretic mobility shift assays, surface plasmon resonance, and RNA affinity purification, my work establishes critical roles for the U1 snRNA stem-loops 3 (SL3) and 4 (SL4) in formation of intron definition interactions during prespliceosome assembly. Previously, the SL4 of the U1 snRNA was shown to form a molecular bridge across introns by contacting the U2-specific splicing factor 3A1 (SF3A1). I identified the Ubiquitin-like domain of SF3A1 as a non-canonical RNA binding domain responsible for U1-SL4 binding. I also determined a role for the SL3 region of the U1 snRNA in splicing and characterized the spliceosomal RNA helicase UAP56 as an SL3 interacting protein. By knocking-down the SL3- and SL4-interacting proteins, I confirmed that U1 splicing activity in vivo relies on UAP56 and SF3A1 and that their functions are interdependent. These findings, in addition to the observations made using in vitro splicing assays, support a model whereby UAP56, through its interaction with U1-SL3, enhances the cross-intron interaction between U1-SL4 and SF3A1 to promote prespliceosome formation.
ContributorsMartelly, William (Author) / Sharma, Shalini (Thesis advisor) / Mangone, Marco (Thesis advisor) / Gustin, Kurt (Committee member) / Chen, Julian (Committee member) / Arizona State University (Publisher)
Created2021
ContributorsCrimminger, Jordan (Performer) / Novak, Gail (Pianist) (Performer) / Hong, Dylan (Performer) / Larson, Ben (Performer) / Russell, Liam (Performer) / Raschko, Hannah (Performer) / ASU Library. Music Library (Publisher)
Created2017-10-22
ContributorsStrickland, Kiefer (Performer) / Novak, Gail (Pianist) (Performer) / McKinch, Riley (Performer) / Hoeckley, Stephanie (Performer) / Bates-Kennard, Sarah (Performer) / Moonitz, Olivia (Performer) / Lovelady, Alexis (Performer) / ASU Library. Music Library (Publisher)
Created2017-10-31
ContributorsProuty, Andre (Performer) / Novak, Gail (Pianist) (Performer) / Holly, Sean (Performer) / Eder, Noah (Performer) / Hazel, Ben (Performer) / Andreoli, Aiden (Performer) / Kurth, Will (Performer) / Peterson, Robert (Performer) / ASU Library. Music Library (Publisher)
Created2022-03-03
ContributorsGerald, Thomas (Performer) / Novak, Gail (Pianist) (Performer) / ASU Library. Music Library (Publisher)
Created2022-02-27
ContributorsGoodman, Mitchell (Performer) / Novak, Gail (Pianist) (Performer) / ASU Library. Music Library (Publisher)
Created2022-02-27
ContributorsMcNamara, Henry (Performer) / Novak, Gail (Pianist) (Performer) / Chea, Alexandra (Performer) / Biswas, Debashis (Performer) / Moreno, Dylan (Performer) / Schay, Adam (Performer) / Meatheads Quartet (Performer) / ASU Library. Music Library (Publisher)
Created2022-02-28
ContributorsStout, Fiona (Performer) / Novak, Gail (Pianist) (Performer) / Austin, Alex (Performer) / ASU Library. Music Library (Publisher)
Created2022-02-24
ContributorsEder, Noah (Performer) / Novak, Gail (Pianist) (Performer) / Kurth, Will (Performer) / ASU Library. Music Library (Publisher)
Created2022-02-26
Description
Biogas’s potential as a renewable fuel source has been an area of increased research in recent years. One issue preventing wide-spread use of biogas as a fuel is the trace amounts of impurities that damage fuel-burning equipment by depositing silicon, sulfur, calcium and other elements on their surface. This study aims to analyze the effects of a high concentration of L4 linear siloxane on solid oxide fuel cell performance until failure occurs. L4 siloxane has not been extensively researched previously, and this investigation aims to provide new data to support similar, though slower, degradation compared to D4, D5 and other siloxanes in solid oxide fuel cells. The experiments were conducted inside a furnace heated to 800℃ with an Ni-YSZ-supported (Nickel-yttria-stabilized zirconia) fuel cell. A fuel source with a flow rate of 20 mL/min of hydrogen gas, 10 mL/min of nitrogen gas and 0.15 mL/min of L4 siloxane was used. Air was supplied to the cathode. The effects of siloxane deposition on cell voltage and power density degradation and resistance increase were studied by using techniques like the current-voltage method, electrochemical impedance spectroscopy, and gas chromatography. The results of the experiment after reduction show roughly constant degradation of 8.35 mV/hr, followed after approximately 8 hours by an increasing degradation until cell failure of 130.45 mV/hr. The initial degradation and stagnation match previous research in siloxane deposition on SOFCs, but the sharp decline to failure does not. A mechanism for solid oxide fuel cell failure is proposed based on the data.
ContributorsRiley, Derall M. (Author) / Milcarek, Ryan J (Thesis advisor) / Wang, Liping (Committee member) / Phelan, Patrick E (Committee member) / Arizona State University (Publisher)
Created2021