Translation initiation from a naturally occurring non-AUG codon in Saccharomyces cerevisiae
Translation initiation from a naturally occurring non-AUG codon in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m311269200
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发表时间：
2004-04-02
影响因子：
4.8
通讯作者：
Wang, CC
中科院分区：
文献类型：
--
作者：
Chang, KJ;Wang, CC
虽然先前的研究已经表明，酿酒酵母中甘氨酰-tRNA合成酶的细胞质和线粒体活性都是由单个基因GRS1提供的，但其发生的机制尚不清楚。这里提供的证据表明，这种双功能特性实际上是由该基因的单个转录本交替产生的两种不同的翻译产物的结果。除了氨基末端的23个氨基酸延伸外，这两种异构体具有相同的多肽序列，并且在正常情况下仅在各自的隔室中发挥作用。报告基因分析进一步表明，该前导肽可以独立地作为线粒体靶向信号发挥作用，并在异构体的亚细胞定位中发挥主要作用。此外，短蛋白是从传统的AUG三联体翻译而来的，而较长的异构体是从上游的基础UUG密码子产生的。据我们所知，GRS1似乎是酵母中第一个从自然产生的非AUG密码子启动功能蛋白亚型的例子。结果表明，非八月启动可能是存在于所有王国的一种机制。
Although previous studies have already shown that both cytoplasmic and mitochondrial activities of glycyl-tRNA synthetase are provided by a single gene, GRS1, in the yeast Saccharomyces cerevisiae, the mechanism by which this occurs remains unclear. Evidence presented here indicates that this bifunctional property is actually a result of two distinct translational products alternatively generated from a single transcript of this gene. Except for an amino-terminal 23-amino acid extension, these two isoforms have the same polypeptide sequence and function exclusively in their respective compartments under normal conditions. Reporter gene assays further suggest that this leader peptide can function independently as a mitochondrial targeting signal and plays the major role in the subcellular localization of the isoforms. Additionally, whereas the short protein is translationally initiated from a traditional AUG triplet, the longer isoform is generated from an upstream inframe UUG codon. To our knowledge, GRS1 appears to be the first example in the yeast wherein a functional protein isoform is initiated from a naturally occurring non-AUG codon. The results suggest that non-AUG initiation might be a mechanism existing throughout all kingdoms.