This item is accessible only to the Washington University community.

Off-Campus WUSTL Users: Click the “Off-Campus Download” button below. You will be prompted to log in using your WUSTL Key.

Date of Award

Spring 2011

Author's School

College of Arts & Sciences

Author's Department/Program



In a rapid response to environmental stress, cellular translation is drastically reduced to conserve energy. The translating pool of mRNAs is sequestered into distinct locations called processing bodies (P-bodies) and can rejoin the translating pool when the stress is removed. Pbodies are ribonucleoprotein complexes composed of an aggregated core of proteins that bind to the non-translating mRNA. P-bodies in yeast consist of eight known protein components, most of which play a role in mRNA degradation by acting as a 5’-decapping enzyme or as a 3’- exonuclease. While the various functions of P-body components have been investigated, the mechanisms of how these P-body components aggregate and how they disaggregate remain largely unknown. We and others have observed that P-bodies in yeast assemble and disassemble at a remarkably rapid rate, hinting at the participation of external factors such as chaperones, which could assist the assembly and dissolution of these structures assembled by aggregation-prone proteins. We hypothesized that the loss or overexpression of specific chaperones could affect Pbody dynamics. Through our deletion screen we identified chaperones that, when deleted, noticeably affect P-body levels within the cell. We found that deletion of the heat shock proteins Hsp104 and Ssa1, as well as a dysfunctional Nascent Chain Associated Complex (NAC), produce changes in overall cellular P-body levels. However, while the deletion of HSP104 and SSA1 result in a general decrease in the ratio of P-body per cell, there is variability in response to NAC changes that depends on the subunit deleted. The rate of P-body disassembly also appeared to be affected by certain NAC subunit deletions. In addition, we discovered chaperones that, when overexpressed, alter P-body dynamics. Mdj1 and Xdj1, heat shock proteins that reside in the mitochondria and are responsible for the proteolysis of aggregated proteins, appeared to decrease cellular P-body levels when overexpressed. On the other hand, Scj1, a heat shock protein inside the ER lumen, caused an increase in the number of P-bodies per cell when overexpressed. Based on our findings, it is likely that some chaperones do play one or more roles in the assembly and dissociation of P-bodies. Although the specific chaperones and their precise functions in P-body dynamics have yet to be clearly elucidated and understood, the presence of chaperones in the P-body assembly and disassembly process would explain the rapid nature of Pbody kinetics and may allow us to generalize the mechanism of P-body assembly to that of other types of protein aggregates.


English (en)

Advisor/Committee Chair

Heather True-Krob