ORCID
https://orcid.org/0009-0001-9574-0241
Date of Award
Spring 2025
Language
English
Embargo Period
4-28-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College/School/Department
Department of Chemistry
Program
Chemistry
First Advisor
Alan Chen
Committee Members
Prof. Andy Berglund Prof. Alexander Shekhtman Prof. Jia Sheng Prof. Mehmet Yigit
Abstract
The post-transcriptional regulation of RNA, particularly through alternative splicing (AS) and chemical modifications, plays a critical role in gene expression and is linked to many human diseases. This thesis investigates three interconnected aspects of RNA and DNA dynamics and their regulation, providing new insights into cellular function.
First, we examine how RNA modifications influence the structural stability of transfer RNA Phenylalanine (tRNAPhe) in S. cerevisiae. Using temperature replica exchange molecular dynamics (T-REMD) simulations, we show that specific modifications create a network of interactions essential for maintaining tRNA’s tertiary structure. Interestingly, magnesium ions (Mg2+) can compensate for the lack of these modifications, highlighting the interplay between RNA modifications, metal ions, and structural stability.
Second, we explore the regulation of insulin receptor (INSR) exon 11 alternative splicing, which is controlled by the proteins MBNL1 and RBFOX1. By using an INSR exon 11 minigene reporter system, we demonstrate that mutations in the RBFOX1 binding site not only disrupt RBFOX1’s function but also affect MBNL1’s ability to regulate splicing. Molecular dynamics simulations reveal how these mutations alter RNA structure, providing a deeper understanding of how splicing factors interact to control gene expression.
Finally, we study the stability of double crossover DNA (DAO) nanostructures in the presence of different ions, including monovalent (Na+, K+) and divalent (Mg2+, Ca2+) ions. Our simulations show that the DAO DNA motif remains stable under various ionic conditions, with divalent ions playing a key role in compacting the structure and bridging DNA helices. These findings highlight the importance of ion type and concentration in DNA nanostructure stability, offering valuable insights for DNA-based nanotechnology applications.
Together, this work bridges the gap between RNA and DNA dynamics, uncovering the complex mechanisms behind alternative splicing, tRNA stability, and DNA nanostructure interactions. The results advance our understanding of nucleic acid biology and open new possibilities for therapeutic strategies and nanotechnology innovations targeting RNA and DNA systems.
License
This work is licensed under the University at Albany Standard Author Agreement.
Recommended Citation
Nowzari, Zohreh, "Exploring RNA Dynamics: Insights into Structural Modifications, Splicing Regulation, and Biological Function" (2025). Electronic Theses & Dissertations (2024 - present). 214.
https://scholarsarchive.library.albany.edu/etd/214
