Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon.
Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon.
复制标题
果蝇 elav 基因座上的两个不同的温度敏感等位基因被同一色氨酸密码子的无义突变抑制。
DOI：
10.1093/genetics/141.3.1101
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发表时间：
1995
期刊：
影响因子：
3.3
通讯作者：
White,K
中科院分区：
文献类型：
--
作者：
Samson,ML;Lisbin,MJ;White,K
果蝇基因 elav 编码正常神经元分化和维持所需的 483 个氨基酸长的核 RNA 结合蛋白。我们对该基因的三个已知的可行等位基因进行了分子分析，即 elavts1、elavFliJ1 和 elavFliJ2，它们表现出温度敏感表型。 elavFliJ1 等位基因的修饰对应于甘氨酸 426 (GGA) 变为谷氨酸 (GAA)。令人惊讶的是，elavts1 和 elavFliJ2 均被发现将色氨酸 419 (TGG) 分别改变为两个不同的终止密码子：TAG 和 TGA。出乎意料的是，elavts1 和 elavFliJ2 的蛋白质分析不仅揭示了由于翻译截短而预测的 45-kD 截短 ELAV 蛋白，而且还揭示了在允许和非允许温度下主要的全尺寸 50-kD ELAV 蛋白。 elavts1 和 elavFliJ2 中存在的全长蛋白可以先验地通过导致无义突变的功能性抑制的几种机制之一来解释，或者通过检测先前未被识别的大小相似的 ELAV 同种型来解释，该同种型由可变剪接产生且不受终止密码子的影响。本文描述的实验支持无义突变的功能性抑制作为全长蛋白质的机制。
The Drosophila gene elav encodes a 483-amino-acid-long nuclear RNA binding protein required for normal neuronal differentiation and maintenance. We molecularly analyzed the three known viable alleles of the gene, namely elavts1, elavFliJ1, and elavFliJ2, which manifest temperature-sensitive phenotypes. The modification of the elavFliJ1 allele corresponds to the change of glycine426 (GGA) into a glutamic acid (GAA). Surprisingly, elavts1 and elavFliJ2 were both found to have tryptophan419 (TGG) changed into two different stop codons, TAG and TGA, respectively. Unexpectedly, protein analysis from elavts1 and elavFliJ2 reveals not only the predicted 45-kD truncated ELAV protein due to translational truncation, but also a predominant full-size 50-kD ELAV protein, both at permissive and nonpermissive temperatures. The full-length protein present in elavts1 and elavFliJ2 can a priori be explained by one of several mechanisms leading to functional suppression of the nonsense mutation or by detection of a previously unrecognized ELAV isoform of similar size resulting from alternative splicing and unaffected by the stop codon. Experiments described in this article support the functional suppression of the nonsense mutation as the mechanism responsible for the full-length protein.