Organisms have had to evolve strategies to survive during fluctuating environmental conditions. One such mechanism of protection during stress, conserved from yeast to mammals, is the transient formation of liquid-like phase transitions, which allows the cell to form membrane-less compartments that create intracellular partitions composed of dense concentrations of proteins and mRNAs. These partitions are thought to acutely regulate the gene expression program by affecting the localization, degradation, storage, and translational capacity of mRNAs during stressful conditions. While protein-RNA interactions are known to drive the formation of these intracellular partitions, less is known about the factors imparting specificity upon the RNAs contained within these granules. Previously, we found that mRNA localization to two such membrane-less compartments, P-bodies and stress granules, was not inherent to the RNA but instead encoded by promoter elements in the nucleus:
Transcriptionally upregulated, well translated HSP26 mRNAs remain diffusely localized during glucose starvation, while transcriptionally upregulated, poorly translated GLC3 mRNAs are sequestered to stress granules. In both cases the promoter is the determining factor in these localization and translation phenotypes.
Our current research is focused on the following specific questions:
  • How does the promoter specify the cytoplasmic fate of an mRNA during stress?
  • What can we learn about the biophysical properties of membrane-less compartments based on the factors specifiying mRNA localization?
  • What consequences does differential mRNA localization have on gene expression during fluctuating environmental conditions?
  • Are there general principles of mRNA localization and gene expression during stressful conditions?
lacZ mRNAs induced pre-starvation are predominantly sequestered to P-bodies, while the same mRNAs induced during glucose starvation are sequestered to stress granules.