Mutations in eukaryotic release factors 1 and 3 act as general nonsense suppressors in Drosophila.
Mutations in eukaryotic release factors 1 and 3 act as general nonsense suppressors in Drosophila.
复制标题
真核释放因子 1 和 3 的突变在果蝇中充当一般的无义抑制因子。
DOI：
10.1093/genetics/165.2.601
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发表时间：
2003
期刊：
影响因子：
3.3
通讯作者：
Bejsovec,Amy
中科院分区：
文献类型：
--
作者：
Chao,AnnaT;Dierick,HermanA;Addy,TracieM;Bejsovec,Amy
在对果蝇无PE4无义等位基因抑制子的筛选中，我们分离出了形成真核释放因子的两个成分的突变。ERF1和eRF3组成翻译终止复合体，识别终止密码子并催化核糖体释放新生的多肽链。破坏果蝇eRF1和eRF3的突变由于停止密码子的通读而显示出强烈的母性效应无稽之谈的抑制，并且在幼虫阶段是合子致死的。我们测试了wg和其他胚胎作用基因中的无义突变，发现不同的终止密码子可以被抑制，但只有部分无义等位基因受到抑制。我们怀疑终止密码子的上下文是重要的：对抑制敏感的无稽之谈的等位基因通过RF1和RF3编码紧随其后的胞苷的终止密码子。这种可抑制的等位基因似乎本质上很弱，当翻译终止被中断时，阅读水平较低，而这种水平会增强。因此，RF1和RF3突变为识别泄漏的无意义等位基因提供了一种工具。我们的发现对分配零突变表型和选择合适的等位基因用于抑制子筛选具有重要意义。
In a screen for suppressors of the DrosophilawinglessPE4nonsense allele, we isolated mutations in the two components that form eukaryotic release factor. eRF1 and eRF3 comprise the translation termination complex that recognizes stop codons and catalyzes the release of nascent polypeptide chains from ribosomes. Mutations disrupting the Drosophila eRF1 and eRF3 show a strong maternal-effect nonsense suppression due to readthrough of stop codons and are zygotically lethal during larval stages. We tested nonsense mutations inwgand in other embryonically acting genes and found that different stop codons can be suppressed but only a subset of nonsense alleles are subject to suppression. We suspect that the context of the stop codon is significant: nonsense alleles sensitive to suppression byeRF1andeRF3encode stop codons that are immediately followed by a cytidine. Such suppressible alleles appear to be intrinsically weak, with a low level of readthrough that is enhanced when translation termination is disrupted. Thus theeRF1andeRF3mutations provide a tool for identifying nonsense alleles that are leaky. Our findings have important implications for assigning null mutant phenotypes and for selecting appropriate alleles to use in suppressor screens.