UC San Diego

The heat shock response has been studied for nearly sixty years. How organisms respond to stress relies on this highly conserved cellular response. However, once a stress is ameliorated, little is understood about how an organism re-sets its molecular landscape. In my thesis, I uncover a role for the microRNA pathway in regulating the molecular re-setting after stress and provide evidence to support its function in promoting survival post stress.The heat shock response (HSR) is a cellular response that has been identified in all species in which it has been studied. The HSR is elicited in response to stressful events including infection, oxidative stress, and heat stress. In my second Chapter, I will discuss how non-coding RNAs, including microRNAs, change expression in response to heat stress in C. elegans. MicroRNAs are small non-coding RNAs that post-transcriptionally repress target mRNA expression. I will detail my work focused on understanding how a specific HS-induced miRNA, miR-239a/b is regulated. As well, I will discuss functional analysis of miR-239a/b performed in an effort to characterize its regulatory roles. In Chapter 3, I will discuss the role of the microRNA pathway during heat shock (HS) recovery. I identified that ALG-1, the predominant Argonaute protein in C. elegans, contributes to survival after heat shock. Furthermore, I unveil a new role for miR-85 in HS recovery in which it acts to downregulate hsp-70, a highly conserved chaperone that is transcriptionally upregulated in response to stress but detrimental when misregulated after stress. Chapter 4 will present evidence of miR-85 mediated regulation of fertility in C. elegans and analysis aimed at addressing mechanistic understanding of this phenotype. Overall, this work deepens our understanding of the role of miRNAs in response to stress.