Year of Award

2026

Document Type

Dissertation - Campus Access Only

Degree Type

Doctor of Philosophy (PhD)

Degree Name

Cellular, Molecular and Microbial Biology

Department or School/College

Division of Biological and Biomedical Sciences

Committee Chair

Bruce Bowler

Commitee Members

Sarah Certel, Stephen Lodmell, Jesse Hay

Keywords

cell cycle, E3 ubiquitin ligase, germ granules, proteasome, RNA-binding proteins, stem and progenitor cells

Abstract

The balance of stem cell proliferation and differentiation is essential for maintaining homeostasis, and elucidating the mechanisms that govern this careful balance facilitates a greater understanding of the causative factors that contribute to cancer, infertility, and aging among other diseases. RNA-binding proteins (RBPs) are critical post-transcriptional regulators of germline stem cell maintenance and here we focus on two highly conserved Pumilio and FBF (PUF) family RBPs, FBF-1 and FBF-2. These RBPs are highly expressed in mitotic germline stem cells of C. elegans and regulate the balance between stem cell proliferation and differentiation. As such, we expect their levels in stem cells to be precisely controlled, but the mechanisms involved in this control are largely unknown. This dissertation uncovers multiple post-translational molecular mechanisms that precisely regulate FBF protein abundance in mitotic germline stem cells. We reveal a multilayered regulatory network that regulates FBF accumulation in response to distinct contexts and constrains FBF levels against aberrant accumulation. We also find that FBF levels are modulated by cell cycle machinery during mitosis. Finally, we use a novel colocalization workflow to analyze FBF-2 subcellular localization and find that its concentration only weakly contributes to its localization. This work reveals a diverse, intricate proteostatic regulatory network that tightly controls FBF levels in germline stem cells. PUF proteins are conserved eukaryotic stem cell regulators and regulate stem cell proliferation and differentiation in many systems. This dissertation broadens our understanding of the mechanisms controlling RBP levels and activity in stem cells that are likely relevant for many other organisms.

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© Copyright 2026 Gabriella Elizabeth Weiss