A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity
A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity
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DOI：
10.1128/jvi.71.9.6416-6426.1997
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发表时间：
1997-09-01
影响因子：
5.4
通讯作者：
Cohen, JB
中科院分区：
文献类型：
--
作者：
Hwang, DY;Cohen, JB
先前对cDNA克隆的分析在人H-ras基因的3'非翻译区中鉴定出一个可选的内含子，观察到未能去除该内含子与该基因的过度表达之间可能存在相关性，表明内含子mag的剪接需要特定的可滴定因子，内含子末端的剪接信号偏离共有序列并且可能效率低下，但我们注意到下游的相邻外显子具有富含嘌呤的区域，让人想起有趣的是，其他基因中富含嘌呤的剪接增强子刺激弱侧翼内含子的去除，我们在此表明，H-ras 的富含嘌呤区域在同源和异源环境中都具有剪接增强子活性。尽管受影响的内含子位于编码区之外，但增强子的倒置或删除使致癌H-ras等位基因的转化活性降低了几倍，用相应的cDNA构建体进行的实验表明，这不是增强子倒置或删除时产生的mRNA结构改变的结果，相反，我们认为该区域除了末端内含子的剪接外还控制着额外的前mRNA加工事件。我们的工作表明，富含嘌呤的区域可能在控制H-ras活性。
Analysis of cDNA clones previously identified an optional intron in the 3'-untranslated region of the human H-ras gene, A possible correlation was observed between failure to remove this intron and overexpression of the gene, suggesting that splicing of the intron mag require a specific titrable factor, The splicing signals at the end of the intron deviate from the consensus and may be inefficient, but we noticed that the adjacent exon downstream has a purine-rich region reminiscent of purine-rich splicing enhancers in other genes that stimulate the removal of weak, flanking introns, We show here that the purine-rich region of H-ras has splicing-enhancer activity in the homologous as well as a heterologous context, Interestingly. although the affected intron is outside the coding region, inversion or deletion of the enhancer reduced the transforming activity of oncogenic H-ras alleles severalfold, Experiments with corresponding cDNA constructs suggested that this is not a consequence of the altered structures of the mRNAs produced when the enhancer is inverted or deleted, Instead, we propose that the region controls an additional pre-mRNA processing event besides splicing of the terminal intron, Our work indicates that the purine-rich region may play an important role in the control of H-ras activity.