The Saccharomyces cerevisae Acetyltransferase NuA4 Regulates Stress Granule Formation in Response to Glucose Deprivation

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Title: The Saccharomyces cerevisae Acetyltransferase NuA4 Regulates Stress Granule Formation in Response to Glucose Deprivation
Authors: Takuski, Jennifer
Date: 2015
Embargo: 2019-12-12
Abstract: When cells are exposed to stress conditions such as heat stress (HS) and glucose deprivation (GD), stress granules (SG) form in the cytoplasm that act to sequester and protect translationally stalled mRNAs from degradation. Presently it is poorly understood how the cell regulates the formation of SGs, however numerous post translational modifications (PTMs) have been detected on SG proteins in both yeast and man, including lysine acetylation. Disruption of lysine deacetylases (KDACs) has been reported to impact SG function in mammalian cells, by an unknown mechanism. Likewise, existing data indicates that the S. cerevisiae lysine acetyltransferase (KAT) NuA4 interacts with and acetylates several SG proteins in-vitro. In this work I demonstrate that NuA4 is required for GD SG assembly, and is involved in regulating SG formation in response to HS and NaN3 treatment. Further, I show that NuA4 is not contributing to GD SG assembly through inhibition of translation initiation, regulation of the glucose sensing pathway Snf1/AMPK, or modulation of Pab1 protein levels. The identification of glucose dependent acetylation sites on Pab1 and the discovery that Pab1 in-vivo acetylation state is dependent on NuA4 implies that acetylation of SG proteins, and Pab1 in particular, maybe a key regulator of assembly. Interestingly, my studies reveal that KDACs inhibit SG formation in unstressed conditions. Collectively this work establishes a role for NuA4 in regulating SG assembly and suggests that lysine acetylation is playing a conserved and critical role in mRNA metabolism.
URL: http://hdl.handle.net/10393/31912
http://dx.doi.org/10.20381/ruor-826
CollectionThèses - Embargo // Theses - Embargo
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