EXPRESSION OF THE H-RAS PROTO-ONCOGENE IS CONTROLLED BY ALTERNATIVE SPLICING
EXPRESSION OF THE H-RAS PROTO-ONCOGENE IS CONTROLLED BY ALTERNATIVE SPLICING
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DOI：
10.1016/0092-8674(89)90427-3
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发表时间：
1989-08-11
期刊：
影响因子：
64.5
通讯作者：
LEVINSON, AD
中科院分区：
文献类型：
--
作者：
COHEN, JB;BROZ, SD;LEVINSON, AD
我们以前证明，在人类H-ras癌基因的最后一个内含子的点突变，导致显着增加的itis的表达和transnasforming效率。在这里，我们建立了这种现象的基础。使用基因重建实验，我们已经确定了一个负作用元件的内含子是完全失活的突变。引入该区域的其他核苷酸改变的影响表明，负元件可能构成选择性外显子。转录本含有这个假定的外显子进行了鉴定和S1核酸酶分析证实，突变阻止其合成。这些转录本的丰度很低，显然是由于信息不稳定和/或有缺陷的处理。替代转录本的预测产物被认为缺乏转化潜力。我们的研究结果表明，选择性剪接正常运作，以抑制p21 H-ras的表达，这种负控制被废除的各种突变，干扰这一进程。
We previously demonstrated that a point mutation in the last intron of the human H-ras oncogene causes a significant increase in itis expression and trnasforming efficiency. Here we establish the basis of this phenomenon. Using gene reconstruction experiments, we have identified a negative-acting element in the intron that is completely inactivated by the mutation. The effects of other nucleotide alterations introduced into this region suggested that the negative element might constitute an alternative exon. Transcripts containing this putative exon were identified and S1 nuclease analysis confirmed that the mutation prevents their synthesis. The abundance of these transcripts is low, apparently due to message instability and/or defective processing. The predicted product of the alternative transcript is suggested to lack transforming potential. Our findings demonstrate that alternative splicing normally operates to suppress p21H-ras expression and that this negative control is abolished by a variety of mutation that interfere with this process.