Date of Award

Spring 1-1-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Min Han

Second Advisor

Tin Tin Su

Third Advisor

Rui Yi

Fourth Advisor

Corrella Detweiler

Fifth Advisor

Roy Parker

Abstract

miRNAs play critical roles in development and other cellular processes in C. elegans even though most individual miRNAs are not essential for development or viability (Miska et al., 2007). Extensive studies in the field have suggested that most miRNA functions are executed through complex miRNA-target interaction networks. Furthermore, such networks may also function semi-redundantly with other regulatory systems to shape gene expression dynamics for proper physiological functions. Hypothesizing that miRNAs function in stress conditions, I collaborated with a postdoctoral fellow to investigate the role of a specific miRNA miR-71 in starvation induced L1 diapause. Hypothesizing that miRNAs collaborate with other gene regulation mechanisms to maintain C. elegans developmental robustness, I, along with another postdoctoral fellow, carried out a genome-wide RNAi screen for genes that interact with the miRNA induced silencing complex (miRISC). We found that when the miRISC is compromised by knocking out one of the two partially redundant GW182 proteins, many genes become essential for development (Weaver et al., 2014). Further analysis of the CED-3 caspase and its interaction with the let-7 family of miRNAs revealed a widely used but previously unknown role in protein degradation, which contrasts the previously known activity of CED-3 in apoptosis. I further focused on a conserved RNA binding protein Vigilin and its interaction with mir-52, which revealed previously unknown roles of Vigilin and miR-52 in larval development. We hypothesize that Vigilin may function with miR-52 and other specific miRNAs to repress a large number of target mRNAs to regulate development. Our results may shed light on the mechanism of how miRNAs work with RNA binding proteins to regulate gene expression for robust development.

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