Glucose depletion inhibits translation initiation via eIF4A loss and subsequent 48S preinitiation complex accumulation, while the pentose phosphate pathway is coordinately up-regulated

Mol Biol Cell. 2011 Sep;22(18):3379-93. doi: 10.1091/mbc.E11-02-0153. Epub 2011 Jul 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Cluster Analysis
  • Eukaryotic Initiation Factor-2B / metabolism
  • Eukaryotic Initiation Factor-4A / metabolism*
  • Eukaryotic Initiation Factor-4G / metabolism
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Glucose / deficiency*
  • Models, Genetic
  • Multiprotein Complexes / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Pentose Phosphate Pathway*
  • Peptide Chain Initiation, Translational*
  • Protein Binding
  • Protein Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Physiological
  • Up-Regulation*

Substances

  • Eukaryotic Initiation Factor-2B
  • Eukaryotic Initiation Factor-4G
  • Multiprotein Complexes
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Eukaryotic Initiation Factor-4A
  • Glucose