UC San Diego

During times of unpredictable stress, organisms must adapt their gene expression to maximize survival. Along with changes in transcription, one conserved means of gene regulation during conditions that quickly represses translation is the formation of cytoplasmic phase-separated mRNP (messenger ribonucleoprotein) granules. Two well-known stress-induced mRNP granules are processing bodies (P-bodies) and stress granules. Previously, we identified that distinct steps in gene expression can be coupled during glucose starvation stress as promoter sequences in the nucleus are able to direct the subcellular localization to or excluded from the phase-separated granules and translatability of mRNAs in the cytosol. During my Ph.D., I have been investigating the underlying mechanisms of how promoter dictates the cytoplasmic fate of mRNAs during glucose starvation. Chapter 1 is a background introduction of the questions I asked. In chapter 2, I led a discovery of a promoter-directed mechanism mediated by AAA+ proteins Rvb1/Rvb2 that couple the transcription, mRNA cytoplasmic localization, and translation of select genes during glucose starvation. In chapter 3, colleagues and I reviewed recent findings regarding stress-related phase-separated granules and shared our insights. Chapter 4 describes 3 projects that aimed to answer the promoter-dictation question from other perspectives, such as expression timing and promoter motifs. Finally, Chapter 5 discusses insights and future directions for my thesis work. I anticipate that these studies will provide us with more insights into complex gene regulation during stressful and pathological conditions.