The protein-coding region of c-myc mRNA contains a sequence that specifies rapid mRNA turnover and induction by protein synthesis inhibitors.
The protein-coding region of c-myc mRNA contains a sequence that specifies rapid mRNA turnover and induction by protein synthesis inhibitors.
复制标题
c-myc mRNA 的蛋白质编码区包含指定快速 mRNA 周转和蛋白质合成抑制剂诱导的序列。
DOI：
10.1101/gad.5.2.232
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发表时间：
1991
影响因子：
10.5
通讯作者：
Lee,W
中科院分区：
文献类型：
--
作者：
Wisdom,R;Lee,W
已知某些mRNA的稳定性受到翻译的影响。一些mRNA似乎通过翻译被保护免于快速降解，而降解与其他mRNA的翻译相关联。这种翻译的选择性效应的分子决定因素是未知的。这种效应的一个例子是在翻译抑制剂存在下诱导早期反应基因mRNA。为了确定蛋白质合成抑制剂诱导早期反应基因mRNA表达的分子基础，我们对早期反应基因家族的一个成员c-myc基因进行了突变分析。我们发现，放线菌酮诱导是由于稳定的c-myc转录。放线菌酮增加c-myc mRNA表达的要求是在mRNA上存在编码c-myc氨基酸335-439的序列，该序列可以被翻译; c-myc基因的所有其他部分都是缺失的，并且该序列可以通过蛋白质合成抑制剂诱导异源基因的mRNA表达。通过在不存在转录阻断药物的情况下直接测量mRNA周转，我们表明该序列可以作为选择性mRNA去稳定元件发挥作用，该元件介导的周转是翻译依赖性的，并且该元件介导的周转被放线菌素D抑制。我们的研究结果支持这一假设，即c-myc mRNA的降解是耦合到翻译，指定这种形式的降解的序列中所包含的蛋白质编码序列，翻译抑制剂诱导c-myc mRNA的表达，通过阻断该元件介导的营业额。
The stability of certain mRNAs is known to be affected by translation. Some mRNAs appear to be protected from rapid degradation by translation, whereas degradation is coupled to translation for other mRNAs. The molecular determinants of this selective effect of translation are unknown. One example of this effect is the induction of early-response gene mRNAs in the presence of translation inhibitors. To define the molecular basis of induction of early-response gene mRNA expression by inhibitors of protein synthesis, we have performed a mutational analysis of one member of the early response gene family, the c-myc gene. We find that induction by cycloheximide is due to stabilization of c-myc transcripts. The requirements for increased expression of c-myc mRNA by cycloheximide are the presence of the sequence encoding c-myc amino acids 335-439 on a mRNA that can be translated; all other portions of the c-myc gene are dispensable, and this sequence can confer induction of mRNA expression by protein synthesis inhibitors on a heterologous gene. By direct measurement of mRNA turnover in the absence of transcription-blocking drugs, we show that this sequence can function as a selective mRNA destabilizing element, that turnover mediated by this element is translation dependent, and turnover mediated by this element is inhibited by actinomycin D. Our results support the hypothesis that degradation of c-myc mRNA is coupled to translation, that the sequences specifying this form of degradation are contained in the protein-coding sequence, and that translation inhibitors induce expression of c-myc mRNA by blocking turnover mediated by this element.