Date of Award
8-2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Genetics and Biochemistry
Committee Chair/Advisor
Lela Lackey
Committee Member
Zhana Duren
Committee Member
Alex Feltus
Committee Member
Heather Flanagan-Steet
Abstract
The SERPINA1 gene encodes the critical protease inhibitor α-1-antitrypsin (A1AT). A1AT represses neutrophil elastase activity to protect lung tissue from inflammatory damage. A deficiency in α-1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD). Pathogenic genetic variants in SERPINA1 are also associated with A1AT protein misfolding and liver cirrhosis. The regulatory mechanisms of SERPINA1 expression are not well understood, but previous studies suggest that alternative polyadenylation in the 3' untranslated region (3'UTR) affects A1AT protein expression. In this study, we used the liver cancer cell line HepG2 to determine how environmental conditions influence SERPINA1 mRNA expression and post-transcriptional regulation. We stimulated HepG2 cells with interleukin-6 (IL-6), ethanol, and peroxide and performed 3' end RNA sequencing. Our findings reveal that IL-6 upregulates distal polyadenylation of SERPINA1 mRNA in HepG2 cells. Additionally, we observed that changes in environmental conditions can lead to alternative polyadenylation in other genes. This study enhances our understanding of how environmental factors, such as IL-6, regulate SERPINA1 expression, particularly through alternative polyadenylation. By clarifying these regulatory mechanisms, this research helps us better understand the development of A1AT related disorders and may guide the creation of new treatments.
Recommended Citation
Jiamutai, FNU, "Regulation of SERPINA1 mRNA Expression by Environmental Conditions in Hepatocyte Cells" (2024). All Theses. 4370.
https://open.clemson.edu/all_theses/4370