Mutations in the structural genes for eukaryotic initiation factors 2 alpha and 2 beta of Saccharomyces cerevisiae disrupt translational control of GCN4 mRNA.
Mutations in the structural genes for eukaryotic initiation factors 2 alpha and 2 beta of Saccharomyces cerevisiae disrupt translational control of GCN4 mRNA.
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酿酒酵母真核起始因子 2α 和 2β 结构基因的突变破坏了 GCN4 mRNA 的翻译控制。
DOI：
10.1073/pnas.86.19.7515
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发表时间：
1989
影响因子：
11.1
通讯作者：
Donahue,TF
中科院分区：
文献类型：
--
作者：
Williams,NP;Hinnebusch,AG;Donahue,TF
酿酒酵母的SUI2和SUI3基因分别编码翻译起始因子eIF-2（真核起始因子2）的α亚基和β亚基。先前在这些基因中分离的突变恢复了his4突变等位基因缺乏ATG起始密码子的表达。SUI突变也导致HIS4 mRNA水平升高。我们发现后一种表型的存在是因为SUI突变提高了GCN4的表达，GCN4是HIS4转录的激活因子。在SUI突变体中，GCN4表达的增加独立于GCN2和GCN3基因产物发生，而GCN2和GCN3基因产物通常是在氨基酸饥饿条件下刺激GCN4 mRNA翻译所必需的。SUI突变体中GCN4表达的抑制需要GCN4转录物前导中的多个AUG密码子，这些密码子通常通过氨基酸可用性介导其翻译控制。在这些方面，SUI突变类似于GCD基因的突变，其产物作为GCN4的翻译抑制因子。因此，除了在AUG启动密码子选择中的一般作用外，eIF-2似乎是GCN4翻译控制的一个重要因素。我们还发现，在sui2-1菌株中，GCN3的缺失是致命的，这表明GCN3除了作为GCN4的翻译激活剂外，还参与了eIF-2 α的功能。
The SUI2 and SUI3 genes of Saccharomyces cerevisiae encode the alpha and beta subunits, respectively, of translation initiation factor eIF-2 (eukaryotic initiation factor 2). Previously isolated mutations in these genes restore expression from his4 mutant alleles lacking an ATG initiation codon. The SUI mutations also lead to increased levels of HIS4 mRNA. We show that the latter phenotype exists because the SUI mutations elevate expression of GCN4, an activator of HIS4 transcription. Increased GCN4 expression in the SUI mutants occurs independently of the GCN2 and GCN3 gene products that are normally required to stimulate translation of GCN4 mRNA under conditions of amino acid starvation. Derepression of GCN4 expression in the SUI mutants requires the multiple AUG codons in the leader of the GCN4 transcript that normally mediate its translational control by amino acid availability. In these respects, the SUI mutations resemble mutations in GCD genes whose products function as translational repressors of GCN4. Thus, in addition to its general role in AUG start codon selection, eIF-2 appears to be an important factor in GCN4 translational control. We also show that deletion of GCN3 in sui2-1 strains is lethal, suggesting that GCN3 contributes to eIF-2 alpha function in addition to its role as a translational activator of GCN4.