Stoneley M, Paulin F E, Le Quesne J P, Chappell S A, Willis A E
Department of Biochemistry, University of Leicester, UK.
Oncogene. 1998 Jan 22;16(3):423-8. doi: 10.1038/sj.onc.1201763.
Translation in eukaryotic cells is generally initiated by ribosome scanning from the 5' end of the capped mRNA. However, initiation of translation may also occur by a mechanism which is independent of the cap structure and in this case ribosomes are directed to the start codon by an internal ribosome entry segment (IRES). Picornaviruses represent the paradigm for this mechanism, but only a few examples exist which show that this mechanism is used by eukaryotic cells. In this report we show data which demonstrate that the 5' UTR of the proto-oncogene c-myc contains an IRES. When a dicistronic reporter vector, with c-myc 5' UTR inserted between the two cistrons, was transfected into both HepG2 and HeLa cells, the translation of the downstream cistron was increased by 50-fold, demonstrating that translational regulation of c-myc is mediated through cap-independent mechanisms. This is the first example of a proto-oncogene regulated in this manner and suggests that aberrant translational regulation of c-myc is likely to play a role in tumorigenesis.
真核细胞中的翻译通常由核糖体从加帽mRNA的5'端开始扫描启动。然而，翻译起始也可能通过一种独立于帽结构的机制发生，在这种情况下，核糖体由内部核糖体进入片段（IRES）引导至起始密码子。微小核糖核酸病毒是这种机制的典型代表，但只有少数例子表明真核细胞使用这种机制。在本报告中，我们展示的数据表明原癌基因c-myc的5'非翻译区（UTR）包含一个IRES。当一个双顺反子报告载体（其两个顺反子之间插入了c-myc 5'UTR）转染到HepG2细胞和HeLa细胞中时，下游顺反子的翻译增加了50倍，这表明c-myc的翻译调控是通过不依赖帽的机制介导的。这是以这种方式调控的原癌基因的首个例子，表明c-myc异常的翻译调控可能在肿瘤发生中起作用。
