Graduation Semester and Year
Summer 2026
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Chemistry
Department
Chemistry and Biochemistry
First Advisor
Dr. Byung Ran So
Second Advisor
Dr. Kayunta Johnson-Winters
Third Advisor
Dr. Joe Buonomo
Fourth Advisor
Dr. He Dong
Abstract
In eukaryotes, precursor messenger RNAs (pre-mRNAs) are transcribed by RNA polymerase II and undergo multiple RNA-processing steps, including 5′ capping, splicing, and 3′-end cleavage and polyadenylation. These processes are tightly regulated by numerous RNA-protein complexes in the nucleus to ensure the production of mature protein-coding mRNAs that are competent for export to the cytoplasm and subsequent translation. Splicing, the process by which noncoding introns are removed, and coding exons are ligated, is catalyzed by a large and dynamic RNA-protein complex known as the spliceosome. The spliceosome is primarily composed of small nuclear ribonucleoproteins (snRNPs), whose assembly, remodeling, and function must be precisely regulated to maintain proper transcript processing and gene expression. The primary focus of my dissertation is to characterize the role of U1C, a U1 snRNP-specific protein, in snRNP biogenesis. In addition, my work examines the functional consequences of mutations in U1 small nuclear RNA (snRNA), including variants identified across multiple cancer types; to better understand how altered U1 snRNP function may contribute to defects in RNA processing and disease-associated gene regulation.
This dissertation is organized into four chapters. Chapter 1 provides a comprehensive overview of pre-mRNA splicing, spliceosome assembly, and the roles of noncoding spliceosomal snRNAs, including U1, U2, U4, U5, U6, and minor snRNAs. It also summarizes disease-associated snRNA mutations identified in cancers and other human disorders and discusses recent therapeutic strategies aimed at correcting spliceosome dysfunction and RNA-processing defects.
Chapter 2 focuses on the role of U1C in snRNP biogenesis through its association with the SMN–Gemin complex. The findings presented in this chapter demonstrate that the C-terminal domain of U1C mediates its interaction with the SMN–Gemin complex and that arginine methylation is required for this association. This chapter also examines cancer-associated U1 snRNA mutations and shows that these mutations disrupt U1C association, impair Sm-core assembly, and reduce cellular snRNP abundance.
Chapter 3 presents characterization of functional regions of U1C. Specifically, this chapter investigates the requirement for basic residues within the N-terminal region of U1C for U1 snRNA binding and explores the contribution of the U1C C-terminal domain to liquid–liquid phase separation.
Chapter 4 discusses ongoing projects focused on developing the dual luciferase reporter system, which monitors gene expression at the transcriptomic and proteomic levels. A collaborative project also focuses on optimizing ribonucleoprotein complex formation and characterizing a chromatographic system to determine lipid nanoparticle encapsulation efficiency.
Keywords
RNA, splicing, transcription regulation, snRNP, snRNA, U1C, snRNA mutation, SMN complex
Disciplines
Biochemistry | Cell Biology | Molecular Biology
License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Ngu, Duc Minh, "FUNCTIONAL CHARACTERIZATION OF U1C AND CANCER-ASSOCIATED U1 SNRNA MUTATIONS IN SNRNP BIOGENESIS" (2026). Chemistry & Biochemistry Dissertations. 13.
https://mavmatrix.uta.edu/chemistry_dissertations2/13
Comments
I would like to sincerely thank my advisor, Dr. Byung Ran So, for her invaluable guidance and mentorship throughout my academic journey, from my early experience as an undergraduate research assistant to my development as a Ph.D. student. I am especially grateful for her confidence in my potential, for the opportunities she provided, and for her unwavering support over the past five years.
I would also like to express my sincere appreciation to my Ph.D. committee members, Dr. Kayunta Johnson-Winters, Dr. Joseph Anthony Buonomo, and Dr. Dong He, for their thoughtful feedback, constructive suggestions, and collaborative contributions throughout my research, which have significantly strengthened this work.
I am grateful to Dr. Zibiao Guo (North Texas Genomics Center), Dr. Jeongsik Yong (University of Minnesota), Dr. Eul Hyun Suh (University of North Texas Health Science Center), and Dr. Ritu Raj (University of North Texas Health Science Center), as well as other collaborators, for their generous support and valuable advice.
My special thanks go to my dedicated lab members, Sanat Myti, Ayesha Ali Khan, and Arunprasath Duraisamy, with whom I have had the privilege to work. You have been not only excellent colleagues but also close friends beyond national boundaries. I truly appreciate your support, guidance, and companionship throughout the past five years of my Ph.D. journey.
I am also grateful for the opportunity to mentor many undergraduate researchers in the lab, including Paul Andega, Jeanne Keita, Jen Chu, Christian Peck, Yae-Lin Kim, Morgan Gresky, Eman Khan, Armeen Nasir, and Rajwi Manandhar. It has been a rewarding experience to share my passion for academic research with them.
I want to thank my friends outside the So laboratory for their friendship and support, especially Dr. Avisankar Chini, Dr. Prathana Guha, Ashcharya Rishi, Nagashree Bhat, Dr. Alaa Aziz, Md Sabid Ahamed, Dr. Arzoo Patel, and Dr. Vo Phan.
I would like to express my sincere appreciation to the dedicated staff, Dr. Roy McDougald, Stephanie Henry, Debbie Cooke, Shelby Adams, and Natalie G. Croy for fostering a supportive environment and maintaining the smooth organization of the program. Special thanks to Dr. Bill Cleaver and Dr. Cynthia Griffith for mentoring me in my role as a teaching assistant.
Finally, I would like to express my deepest gratitude to my family. I am forever indebted to my parents, Vinh Ngu and Phi Chau, for their unwavering support, sacrifices, and belief in me. They have given me every opportunity to pursue my education abroad and to achieve possibilities they did not have themselves. I am truly and eternally grateful. I would also like to thank my sister, Ky Ngu, and everyone who has been part of my journey for their support and for helping shape who I am today. My heartfelt thanks go to my girlfriend, Nhu Nguyen for her emotional support, love, and encouragement, which have helped me continue growing and striving forward each day.
This journey has been an unforgettable experience that has provided me with the knowledge and wisdom to carry forward throughout my life.