Publication Date
2022
Document Type
Thesis
Committee Members
Shulin Ju, Ph.D. (Advisor); Labib Rouhana, Ph.D. (Committee Member); Quan Zhong, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
ALS is a neurodegenerative disease characterized by degeneration of upper and lower motor neurons in the brain and spinal cord leading to progressive paralysis and ultimately death. Perturbations in RNA metabolism and RNA binding proteins have emerged as underlying defects in ALS pathogenesis. Matrin-3 is a multifunctional RNA binding protein that has been linked to familial and sporadic ALS. Matrin-3 is normally found in the nucleus, but mutations in the gene cause mislocalization of the protein from the nucleus into the cytoplasm of neuronal cells where it forms protein aggregates. In this study, we show that over-expressing human MATR3 in the budding yeast, Saccharomyces cerevisiae, results in cellular toxicity and cytoplasmic aggregation, recapitulating phenotypes of mutant Matrin-3 in mammalian models and patients. We tested Matrin-3 with other ALS-associated RBPs and identified human genes that rescue cells from Matrin-3-induced growth defects without altering protein aggregation patterns.
Page Count
86
Department or Program
Department of Biological Sciences
Year Degree Awarded
2022
Copyright
Copyright 2022, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
