Glucose depletion inhibits translation initiation via eIF4A loss and subsequent 48S preinitiation complex accumulation, while the pentose phosphate pathway is coordinately up-regulated.
Glucose depletion inhibits translation initiation via eIF4A loss and subsequent 48S preinitiation complex accumulation, while the pentose phosphate pathway is coordinately up-regulated.
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DOI：
10.1091/mbc.e11-02-0153
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发表时间：
2011-09
影响因子：
3.3
通讯作者：
Ashe MP
中科院分区：
文献类型：
--
作者：
Castelli LM;Lui J;Campbell SG;Rowe W;Zeef LA;Holmes LE;Hoyle NP;Bone J;Selley JN;Sims PF;Ashe MP
研究了酵母中葡萄糖消耗引起的翻译抑制的机制和后果。eIF4A从起始前复合物中丢失，并且戊糖磷酸途径被翻译上调，从而允许有效地过渡到新的条件。细胞应激可以全面抑制翻译起始，从酵母中去除葡萄糖在速度和规模方面引起最显著的影响之一。在这里，我们表明，在酵母生长过程中，随着葡萄糖水平的降低，同样的快速抑制也会发生。我们描述了这种新的调控，表明它涉及48S预起始复合体的改变。特别是，eIF4A和eIF4G之间的相互作用不稳定，导致eIF3-eIF4G在48S复合物上的相互作用暂时稳定。在这种条件下，对适应新条件很重要的特定mrna必须继续被翻译。我们已经确定了哪些mrna在葡萄糖饥饿后早期仍被翻译。这些实验使我们能够通过归因于翻译维持或上调的定义功能，为这种翻译调节提供生理背景。在这类mRNA中，涉及碳水化合物代谢的mRNA数量过多，包括来自戊糖磷酸途径的几种mRNA。我们的数据支持一种假设，即戊糖磷酸途径的协同抢先激活，其目标是mRNA转录和翻译，对于酵母从发酵生长到呼吸生长的转变很重要。
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.