MODELING THE IMPACTS OF 2-AMINOPURINE ON RNA BINDING AFFINITY AND STRUCTURAL DISRUPTIONS VIA FLUORESCENCE SPECTROSCOPY
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Date
2022
Authors
Galutera, Dylan
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Journal ISSN
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Publisher
University of Oregon
Abstract
Within bacteria, Riboswitches function as regulatory RNA that components that control the gene expression of an mRNA by responding to a ligand and causing conformational changes to the riboswitch. The growing knowledge of riboswitches and their implications on mRNA regulation of gene expression shows promises in future therapeutic targets. A current issue with antibiotic therapies is the dangers associated with increasing antibiotic resistance in certain bacteria so the field of study of non- antibacterial therapeutic targets is ever growing. Non-antibacterial therapeutic targets are potential mechanisms for executing the same antibacterial activity as traditional antibiotics, but the bacteria does not develop resistance as it is not a traditional antibiotic. It has been hypothesized that bacterial death can be induced when enough non-essential genes are turned off by controlling the conformation of the riboswitch that regulates the different mRNAs. Although there is a lot of promise in developing riboswitches as therapeutic target without increasing antibacterial resistance, there is still a lot to be understood and learned regarding the fundamentals of riboswitches and their folding dynamics. In this study, we aim to resolve discrepancies in existing literature for the folding dynamics of a riboswitch that senses the ligand preQ1 where one source demonstrates the riboswitch maintaining as single conformation regardless of the ligand’s presence while another source shows dynamic conformational responses to the ligand. A clearer understanding of these fundamental elements of riboswitches is required to further the field of its efficacy as a non-antibacterial therapeutic target. We show in this study that the fluorescent base analogue 2-aminopurine can be used as a probe to study the local structural changes of the preQ1 riboswitch in response to a ligand. Future optimization is required to resolve the discrepancy found in existing literature, but current methods discussed here shows promise in resolving these issues.
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Keywords
preQ1 riboswitch, Fluorescence Spectroscopy, Dissociation constant, 2-aminopurine, RNA