DOI

10.1093/g3journal/jkaf307Ded1p 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.

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 HAT1antagonizes the accumulation of P-bodies under short-term stresses. Under sustained glucose deprivation during the stationary phase, strains lacking HAT1form 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.

Document Type

Article

Publication Date

12-19-2025

Publisher Statement

© The Author(s) 2025. Published by Oxford University Press on behalf of The Genetics Society of America.   This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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