Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Molecular Biophysics and Biochemistry
First Advisor
Strobel, Scott
Abstract
Recognizing and responding to environmental stimuli is essential for organisms across all domains of life. Riboswitches sense environmental stimuli in the form of a small molecule ligand and then structurally rearrange to modulate gene expression in response. Specific ligand recognition is, therefore, a requirement of a functional riboswitch. This dissertation focuses on relating the primary sequence of a riboswitch to a role in ligand specificity. Unlike structural studies, which are used to identify nucleotides in direct ligand contact, I have taken a mutational approach to determine which nucleotides, when mutated, alter riboswitch function or ligand specificity. I focus on variant riboswitches where a small number of sequence changes can change the ligand specificity. I seek to understand how specificity is achieved in closely related variant systems. Peripheral nucleotides and the expression platform both impact ligand specificity in variant riboswitches as well as nucleotides that directly interact with the ligand. In addition to informing on the sequence requirements for specific ligand interaction, this investigation has led to the discovery of a new ykkC variant class as well as the development of potential synthetic pyrimidine-containing cyclic dinucleotide riboswitches.
Recommended Citation
Barth, Kathryn, "Investigating the Sequence Requirements for Specific Ligand Recognition in Variant Riboswitches" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1336.
https://elischolar.library.yale.edu/gsas_dissertations/1336
