Date of Award
Spring 2024
Document Type
Thesis (Master's)
Department or Program
Biochemistry and Cell Biology
First Advisor
Soni Lacefield
Abstract
Meiosis or gametogenesis is a specialized cell division that produces gametes in sexually reproducing organisms. The process of meiosis reduces the genetic content into half that of the progenitor cell. This reduction in the genetic content occurs over a set of two divisions: meiosis I and meiosis II. Because gametes are essential for propagation of life, meiosis operates under tight regulation ensuring the full functionality and viability of the gametes produced. The working principle of the regulatory network that restricts meiosis to only two divisions is not clearly understood. Budding yeast undergoes meiosis in response to starvation. Autophagy being a common cellular degradation and recycling process, is an expected response to starvation. Previous work showing poor meiotic progression in autophagy mutants questions the role of autophagy during meiosis of budding yeast. Recent findings from the Lacefield lab highlights the importance of autophagy for an irreversible meiotic termination. Disruption of autophagy prevents the cells from exiting the meiotic cell cycle after anaphase II, causing them to undergo extra aberrant divisions. Work done in the Lacefield lab showed Rim4, an RNA binding protein, to be an important target of autophagy during meiosis. Recent findings from the Amon and Berchowitz labs showed Rim4 to be a substrate of meiosis specific Ime2 kinase. Ime2 mediated phosphorylation of Rim4 is thought to signal the degradation of Rim4 at the onset of meiosis II, releasing the bound mRNAs, during meiosis II. Translation of the Rim4 bound mRNAs is important for the meiotic exit. Our work reveals the working of a meiotic exit regulatory network driven by autophagy. We show that autophagy inhibition lowers the abundance of meiosis specific proteins which interferes with the process of meiotic termination. We show that Ime2 kinase, which is lowered with autophagy inhibition, is a key player in the regulatory network. Our observations broadly indicate that timely phosphorylation of Rim4 by Ime2 kinase is essential for allowing translation of the bound mRNAs, even in the absence of autophagy. Improper functioning of Ime2 kinase together with insufficient phosphorylation of Rim4 upsets the expression profile of meiotic regulators like transcription factors, kinases and cyclins, which prevents the irreversible meiotic exit.
Recommended Citation
Paul, Somdutta, "Autophagy and Ime2 kinase in regulation of meiotic exit in Saccharomyces cerevisiae" (2024). Dartmouth College Master’s Theses. 169.
https://digitalcommons.dartmouth.edu/masters_theses/169