READING-FRAME RESTORATION WITH AN APOLIPOPROTEIN-B GENE FRAMESHIFT MUTATION
READING-FRAME RESTORATION WITH AN APOLIPOPROTEIN-B GENE FRAMESHIFT MUTATION
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DOI：
10.1073/pnas.89.23.11431
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发表时间：
1992-12-01
影响因子：
11.1
通讯作者：
YOUNG, SG
中科院分区：
文献类型：
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作者：
LINTON, MF;PIEROTTI, V;YOUNG, SG
我们研究了一种导致低β脂蛋白血症的人载脂蛋白B（apoB）突变等位基因，该基因在外显子26中有一个胞嘧啶缺失。这种移码突变与预测大小的截短型apoB蛋白的合成有关；然而，对人类受试者的研究以及在培养细胞中的小基因表达研究表明，该突变等位基因也能产生一种全长的apoB蛋白。突变的apoB等位基因中1个碱基对的缺失产生了一段连续8个腺嘌呤的序列。为了了解突变的apoB等位基因产生全长apoB蛋白的机制，对用突变的apoB小基因表达载体转染的细胞的cDNA进行了检测。mRNA的剪接是正常的；然而，11%的cDNA克隆在8个腺嘌呤序列中多了一个腺嘌呤，产生了连续9个腺嘌呤。额外腺嘌呤的插入（推测是在apoB基因转录过程中）预计会恢复正确的apoB阅读框，从而允许合成全长的apoB蛋白。
We examined a mutant human apolipoprotein B (apoB) allele that causes hypobetalipoproteinemia and has a single cytosine deletion in exon 26. This frameshift mutation was associated with the synthesis of a truncated apoB protein of the predicted size; however, studies in human subjects and minigene expression studies in cultured cells indicated that the mutant allele also yielded a full-length apoB protein. The 1-base-pair deletion in the mutant apoB allele created a stretch of eight consecutive adenines. To understand the mechanism whereby the mutant apoB allele yielded a full-length apoB protein, the cDNA from cells transfected with the mutant apoB minigene expression vector was examined. Splicing of the mRNA was normal; however, 11% of the cDNA clones had an additional adenine within the stretch of eight adenines, yielding nine consecutive adenines. The insertion of the extra adenine, presumably during apoB gene transcription, is predicted to restore the correct apoB reading frame, thereby permitting the synthesis of a full-length apoB protein.