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Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs

Ded1 is an essential DEAD-box helicase in yeast that broadly stimulates translation initiation and is critical for mRNAs with structured 5′UTRs. Recent evidence suggests that the condensation of Ded1 in mRNA granules down-regulates Ded1 function during heat-shock and glucose starvation. We examined...

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Autores principales: Sen, Neelam Dabas, Zhang, Hongen, Hinnebusch, Alan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706886/
https://www.ncbi.nlm.nih.gov/pubmed/34946015
http://dx.doi.org/10.3390/microorganisms9122413
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author Sen, Neelam Dabas
Zhang, Hongen
Hinnebusch, Alan G.
author_facet Sen, Neelam Dabas
Zhang, Hongen
Hinnebusch, Alan G.
author_sort Sen, Neelam Dabas
collection PubMed
description Ded1 is an essential DEAD-box helicase in yeast that broadly stimulates translation initiation and is critical for mRNAs with structured 5′UTRs. Recent evidence suggests that the condensation of Ded1 in mRNA granules down-regulates Ded1 function during heat-shock and glucose starvation. We examined this hypothesis by determining the overlap between mRNAs whose relative translational efficiencies (TEs), as determined by ribosomal profiling, were diminished in either stressed WT cells or in ded1 mutants examined in non-stress conditions. Only subsets of the Ded1-hyperdependent mRNAs identified in ded1 mutant cells exhibited strong TE reductions in glucose-starved or heat-shocked WT cells, and those down-regulated by glucose starvation also exhibited hyper-dependence on initiation factor eIF4B, and to a lesser extent eIF4A, for efficient translation in non-stressed cells. These findings are consistent with recent proposals that the dissociation of Ded1 from mRNA 5′UTRs and the condensation of Ded1 contribute to reduced Ded1 function during stress, and they further suggest that the down-regulation of eIF4B and eIF4A functions also contributes to the translational impairment of a select group of Ded1 mRNA targets with heightened dependence on all three factors during glucose starvation.
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spelling pubmed-87068862021-12-25 Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs Sen, Neelam Dabas Zhang, Hongen Hinnebusch, Alan G. Microorganisms Article Ded1 is an essential DEAD-box helicase in yeast that broadly stimulates translation initiation and is critical for mRNAs with structured 5′UTRs. Recent evidence suggests that the condensation of Ded1 in mRNA granules down-regulates Ded1 function during heat-shock and glucose starvation. We examined this hypothesis by determining the overlap between mRNAs whose relative translational efficiencies (TEs), as determined by ribosomal profiling, were diminished in either stressed WT cells or in ded1 mutants examined in non-stress conditions. Only subsets of the Ded1-hyperdependent mRNAs identified in ded1 mutant cells exhibited strong TE reductions in glucose-starved or heat-shocked WT cells, and those down-regulated by glucose starvation also exhibited hyper-dependence on initiation factor eIF4B, and to a lesser extent eIF4A, for efficient translation in non-stressed cells. These findings are consistent with recent proposals that the dissociation of Ded1 from mRNA 5′UTRs and the condensation of Ded1 contribute to reduced Ded1 function during stress, and they further suggest that the down-regulation of eIF4B and eIF4A functions also contributes to the translational impairment of a select group of Ded1 mRNA targets with heightened dependence on all three factors during glucose starvation. MDPI 2021-11-23 /pmc/articles/PMC8706886/ /pubmed/34946015 http://dx.doi.org/10.3390/microorganisms9122413 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sen, Neelam Dabas
Zhang, Hongen
Hinnebusch, Alan G.
Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
title Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
title_full Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
title_fullStr Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
title_full_unstemmed Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
title_short Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
title_sort down-regulation of yeast helicase ded1 by glucose starvation or heat-shock differentially impairs translation of ded1-dependent mrnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706886/
https://www.ncbi.nlm.nih.gov/pubmed/34946015
http://dx.doi.org/10.3390/microorganisms9122413
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AT hinnebuschalang downregulationofyeasthelicaseded1byglucosestarvationorheatshockdifferentiallyimpairstranslationofded1dependentmrnas