Advisor(s)
Jun Zhang
Committee Member(s)
Aaron Lucius
Hui-Ting Lee
William Placzek
Xinyang Zhao
School
College of Arts and Sciences
Document Type
Dissertation
Department (new version)
Chemistry
Date of Award
1-6-2025
Abstract
The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions that support splicing transitions. In chapters 2 and 3, buffer components are designed to compete selectively for unwanted intermolecular interactions, enabling NMR spectra to be obtained. In chapters 3 and 4, we use these techniques to gain insight into SRSF1’s phase separation and to construct models of its major phosphorylation states. Finally, we relate these models to ligand binding affinities, providing insights into how spliceosome assembly and activation are regulated by SR protein phosphorylation.
ProQuest ID
Recommended Citation
Fargason, Talia, "Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate" (2025). All ETDs from UAB. 7279.
https://digitalcommons.library.uab.edu/etd-collection/7279
