Nonsense mutations and diminished mRNA levels
Nonsense mutations and diminished mRNA levels
复制标题
无义突变和 mRNA 水平降低
DOI：
10.1038/ng0793-219
复制
发表时间：
1993
期刊：
影响因子：
30.8
通讯作者：
H. Dietz
中科院分区：
文献类型：
--
作者：
I. Mcintosh;A. Hamosh;H. Dietz
Sir-尽管有越来越多的相反证据，但仍然普遍认为提前终止密码子（PTC）的主要后果是产生截短的多肽1 -3。在大多数情况下，PTC的主要后果是来自突变等位基因4-<>的mRNA水平的严重降低。在模型系统中，只有当PTC位于末端外显子或倒数第二个外显子的末端三分之一时，突变体转录物的正常水平才得以保留。在大多数情况下，含有PTC的mRNA在细胞质中以降低的水平存在，并且已经提出了解释这种现象的模型7。在”翻译易位”模型中，细胞质中的翻译机制将mRNA拉过核膜。”核扫描”模型预测存在在易位之前扫描mRNA的终止密码子的手段。前一种模型与最后外显子中的PTC允许mRNA易位和翻译的观察结果更一致，而后者更容易适应观察到的含有终止密码子的组成型外显子的跳跃8。可能的是，可以采用两者的组合，并且两者都不是100%有效的。因此在体内观察到少量的自然基因组卷1993年7月4日的通信记录4 - 8·在大多数情况下，由含有PTC的等位基因产生的蛋白质的水平尚未确定，尽管由于mRNA的严重减少，预计其量会减少。PTC（和截短的蛋白质）的影响可能会在显性和隐性疾病之间有所不同。在隐性疾病中，正常功能蛋白质水平的降低可能足以引起疾病4 -6。这也可能适用于选定的
Sir-Despite mounting evidence to the contrary, there is still a widespread belief that the predominant consequence of a premature termination codon (PTC) is the production of a truncated polypeptide1-3• In a majority of instances, the primary consequence of a PTC is a severe reduction in the level of mRNA from the mutant allele4-<>. In model systems, a normal level of mutant transcript is only retained when the PTC is in the terminal exon or terminal-third of the penultimate exon. In most cases, mRNA containing a PTC is present at reduced levels in the cytoplasm and models have been proposed to explain this phenomenon7• In the" translational translocation" model, the translational machinery in the cytoplasm pulls the mRNA through the nuclear membrane. The" nuclear scanning" model predicts the existence of a means of scanning the mRN A for termination codons prior to translocation. The former model is more consistent with the observation that PTCs in the final exon allow translocation of mRNA and translation, whereas the latter more readily accommodates the observed skipping of constitutive exons containing termination codons8• It is possible that a combination of both may be employed and that neither is 100% effective, hence the small amounts of nature genencs volume 4 july 1993 correspondence transcript observed in vivo4-<>· 8•In most cases, the level of protein produced from an allele containing a PTC has not been determined although a reduced amount would be expected due to the severe reduction in mRNA. The effect of PTCs (and truncated protein) might be expected to differ between dominant and recessive diseases. In recessive conditions the reduction in levels of normally functioning protein are probably sufficient to cause disease4-6. This may also be true for selected