Glucose depletion inhibits translation initiation via eIF4A loss and subsequent 48S preinitiation complex accumulation, while the pentose phosphate pathway is coordinately up-regulated
| Autor: | Jonathon Bone, Julian N. Selley, Mark P. Ashe, Jennifer Lui, Nathaniel P. Hoyle, Lydia M. Castelli, Paul F. G. Sims, Susan G. Campbell, William Rowe, Leah E. A. Holmes, Leo A. H. Zeef |
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| Rok vydání: | 2011 |
| Předmět: |
Cell Physiology
Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae Gene Expression Biology Pentose phosphate pathway Pentose Phosphate Pathway 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Eukaryotic translation Stress Physiological Gene Expression Regulation Fungal Translational regulation Cluster Analysis RNA Messenger Peptide Chain Initiation Translational Molecular Biology Oligonucleotide Array Sequence Analysis 030304 developmental biology 0303 health sciences Models Genetic Protein Stability EIF4G Gene Expression Profiling Articles Cell Biology biology.organism_classification Adaptation Physiological Yeast Up-Regulation Eukaryotic Initiation Factor-2B Glucose chemistry Biochemistry Multiprotein Complexes eIF4A Eukaryotic Initiation Factor-4A Transcription preinitiation complex Eukaryotic Initiation Factor-4G 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e11-02-0153 |
| Popis: | The mechanism and consequences of the translational inhibition caused by glucose depletion in yeast are characterized. eIF4A is lost from the preinitiation complex, and the pentose phosphate pathway is translationally up-regulated, allowing an efficient transition to the new conditions. Cellular stress can globally inhibit translation initiation, and glucose removal from yeast causes one of the most dramatic effects in terms of rapidity and scale. Here we show that the same rapid inhibition occurs during yeast growth as glucose levels diminish. We characterize this novel regulation showing that it involves alterations within the 48S preinitiation complex. In particular, the interaction between eIF4A and eIF4G is destabilized, leading to a temporary stabilization of the eIF3–eIF4G interaction on the 48S complex. Under such conditions, specific mRNAs that are important for the adaptation to the new conditions must continue to be translated. We have determined which mRNAs remain translated early after glucose starvation. These experiments enable us to provide a physiological context for this translational regulation by ascribing defined functions that are translationally maintained or up-regulated. Overrepresented in this class of mRNA are those involved in carbohydrate metabolism, including several mRNAs from the pentose phosphate pathway. Our data support a hypothesis that a concerted preemptive activation of the pentose phosphate pathway, which targets both mRNA transcription and translation, is important for the transition from fermentative to respiratory growth in yeast. |
| Databáze: | OpenAIRE |
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