UC San Diego

Only ~one percent of the genome is protein coding. This finding led to the belief that much of the non-coding genome is junk DNA. However, we now understand that much of the non-coding genome is transcribed to some extent. This knowledge coupled with the fact that some RNAs transcribed from non-coding regions of the genome (ncRNA) are involved in important biological processes, has shattered the notion that the non-coding portion of the genome is simply detritus. In my thesis, I explore the role of various classes of non-coding RNAs in the response to Heat Stress.

In Chapter 2, I review miRNA biogenesis. MicroRNAs undergo a complex biogenesis process in order to be processed into mature miRNAs capable of gene regulation. The steps of miRNA biogenesis are tightly regulated, and perturbations in them are associated with disease. MicroRNAs appear to play especially critical roles in the nervous system, and in Chapter 2 I focus on examples of how differentially regulated or misregulated miRNA biogenesis can affect the function of the nervous system. Chapter 3 focuses on my analysis of miRNAs and additional ncRNAs in the C. elegans Heat Shock Response (HSR). The HSR has been studied for over fifty years, yet there is a dearth of information considering the roles of ncRNAs in the HSR. I explore how different classes of ncRNAs, including miRNAs, are differentially regulated in HS in C. elegans. Interestingly, I show that some specific ncRNAs are regulated by Heat Shock Factor 1 (HSF-1), which is a conserved transcription factor that is responsible for the upregulation of specific genes in HS. These results illustrate that ncRNAs likely play important roles in the HSR.

MicroRNAs are also implicated in C. elegans aging. The C. elegans Argonaute proteins, ALG-1 and ALG-2, which are guided by miRNAs to mRNAs to repress gene expression are also implicated in aging. In Chapter 4, I detail my analysis on identifying targets of miRNAs that are associated with either ALG-1 or ALG-2 miRNA mediated regulation in aging.