Yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for the rapid reprogramming of translation after hyperosmotic shock
Yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for the rapid reprogramming of translation after hyperosmotic shock
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DOI：
10.1091/mbc.e11-05-0419
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Alepuz, Paula
中科院分区：
文献类型：
--
作者：
Garre, Elena;Romero-Santacreu, Lorena;Alepuz, Paula
作为对渗透胁迫的反应，整体翻译被抑制，但编码应激保护蛋白的mRNAs被选择性地翻译以允许细胞存活。到目前为止，酿酒酵母中渗透胁迫反应基因的特异性翻译的机制和因素尚不清楚。我们发现，mRNA帽结合蛋白Cbc1对于酵母在渗透胁迫下的生存是重要的。我们的结果为Cbc1在翻译启动中的作用提供了新的证据。Cbc1与多聚体相关，而CBc1基因的缺失会导致对翻译抑制剂放线菌亚胺的超敏反应，并在翻译启动因子eIF4E含量有限的细胞中产生合成的“疾病”。在cbc1 Delta突变体中，在渗透胁迫下，翻译急剧下降，随后的翻译重新启动被推迟，含有未翻译的mRNAs的“加工体”长期存在。此外，在cbc1 Delta细胞中，渗透胁迫反应的mRNAs在渗透胁迫后被转录诱导，但它们与多聚体的快速结合被推迟。然而，在含有温度敏感的eif4E等位基因的细胞中，它们在37℃下不能生长的能力受到高渗透的抑制，Cbc1从细胞核重新定位到细胞质。这些数据支持这样一个模型，即eIF4E翻译可能是胁迫敏感的，而Cbc1介导的翻译是渗透胁迫下渗透胁迫保护蛋白快速翻译所必需的。
In response to osmotic stress, global translation is inhibited, but the mRNAs encoding stress-protective proteins are selectively translated to allow cell survival. To date, the mechanisms and factors involved in the specific translation of osmostress-responsive genes in Saccharomyces cerevisiae are unknown. We find that the mRNA cap-binding protein Cbc1 is important for yeast survival under osmotic stress. Our results provide new evidence supporting a role of Cbc1 in translation initiation. Cbc1 associates with polysomes, while the deletion of the CBC1 gene causes hypersensitivity to the translation inhibitor cycloheximide and yields synthetic "sickness" in cells with limiting amounts of translation initiator factor eIF4E. In cbc1 Delta mutants, translation drops sharply under osmotic stress, the subsequent reinitiation of translation is retarded, and "processing bodies" containing untranslating mRNAs remain for long periods. Furthermore, osmostress-responsive mRNAs are transcriptionally induced after osmotic stress in cbc1 Delta cells, but their rapid association with polysomes is delayed. However, in cells containing a thermosensitive eIF4E allele, their inability to grow at 37 degrees C is suppressed by hyperosmosis, and Cbc1 relocalizes from nucleus to cytoplasm. These data support a model in which eIF4E-translation could be stress-sensitive, while Cbc1-mediated translation is necessary for the rapid translation of osmostress-protective proteins under osmotic stress.