# A genetic interaction between DED1 and HAT1 in Saccharomyces cerevisiae reveals a role for Hat1p in cytoplasmic RNA granule accumulation

## TL;DR

This study finds a genetic link between DED1 and HAT1 in yeast, showing how HAT1 influences RNA granule formation and cell survival under stress.

## Contribution

The study identifies HAT1 as a regulator of DED1 and cytoplasmic RNA granules, revealing a novel role for acetylation in mRNA storage and translation.

## Key findings

- Overexpression of HAT1 suppresses the growth defect caused by DED1 overexpression in yeast.
- HAT1 antagonizes P-body accumulation under short-term stress and affects stress granule formation during glucose deprivation.
- Multiple lysine acetyltransferases and deacetylases are identified as potential regulators of mRNA storage and translation.

## Abstract

Ded1p is an essential translation initiation factor that interacts with and is modulated by eIF4F. Ded1p also promotes the assembly and disassembly of stress granules, which contain nontranslating mRNAs and translation initiation factors. As Ded1p affects both mRNA storage and translation initiation, regulation of Ded1p's function may affect whether mRNAs are translated or localized to cytoplasmic RNA granules. To identify regulators of Ded1p in Saccharomyces cerevisiae, we screened for overexpression suppressors of the severe growth defect conferred by high levels of Ded1p. We found that overexpression of HAT1, a lysine acetyltransferase, can suppress the growth defect conferred by overexpression of DED1, but we do not find evidence of direct acetylation. We demonstrate that HAT1 antagonizes the accumulation of P-bodies under short-term stresses. Under sustained glucose deprivation during the stationary phase, strains lacking HAT1 form more stress granules and have a survival advantage. Given the genetic connection between HAT1 and DED1, we screened for other lysine acetyltransferases and deacetylases that have a genetic interaction with DED1, identifying several more of these post-translational modifiers as possible regulators of mRNA storage and/or translation. These results demonstrate connections between acetylation and the control of cytoplasmic mRNA localization.