Temporal Dynamics of mRNP Granules in Relation to Cellular Metabolic State

Ut Southwestern Medical Center, Dallas TX

Investigators

Abstract

DESCRIPTION (provided by applicant): Under stress, eukaryotic cells repress translation and aggregate mRNAs into cytoplasmic mRNP-granules termed stress-granules and p-bodies. Much remains unknown about the functional significance of these granules. I propose to investigate these mRNP-granules by utilizing the yeast metabolic cycle (YMC) system where the metabolic state of the cell is precisely coordinated with synchronous changes in mRNA transcription, translation, and metabolism. My preliminary results suggest that mRNP granules dynamically form and disassemble throughout the YMC. Herein, I propose to dissect the role of mRNP granules in mediating the changes to mRNA levels brought about by metabolic cycling. Using a combination of robust biochemical, LC/MS/MS, and RNA-seq based techniques, I will determine the RNA and the protein contents of these mRNP granules and investigate whether any 'signature' posttranslational modification of the granule proteins is associated with granule formation or disassembly. By genetically disrupting formation of mRNP granules, I will further determine how they coordinate mRNA and protein expression with each stage of the cycle. Lastly, I will investigate whether, and how, the association of mRNAs with mRNP granules dictates their entry into, and escape from, the active translation pool as a function of the metabolic state of the cell.