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首页> 外文期刊>Molecular and Cellular Biology >c-myc Internal Ribosome Entry Site Activity Is Developmentally Controlled and Subjected to a Strong Translational Repression in Adult Transgenic Mice
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c-myc Internal Ribosome Entry Site Activity Is Developmentally Controlled and Subjected to a Strong Translational Repression in Adult Transgenic Mice

机译：c-myc内部核糖体进入位点的活动受到发展控制，并在成年转基因小鼠中受到强烈的翻译抑制。

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The expression of c-myc proto-oncogene, a key regulator of cell proliferation and apoptosis, is controlled at different transcriptional and posttranscriptional levels. In particular, the c-myc mRNA contains an internal ribosome entry site (IRES) able to promote translation initiation independently from the classical cap-dependent mechanism. We analyzed the variations of c-myc IRES activity ex vivo in different proliferating cell types, and in vivo in transgenic mice expressing a bicistronic dual luciferase construct. c-myc IRES efficiency was compared to that of encephalomyocarditis virus (EMCV) IRES under the same conditions. The c-myc IRES was active but with variable efficiency in all transiently transfected cell types; it was also active in the 11-day- old (E11) embryo and in some tissues of the E16 embryo. Strikingly, its activity was undetected or very low in all adult organs tested. In contrast, EMCV IRES was very active in most cell types ex vivo, as well as in embryonic and adult tissues. These data suggest a crucial role of IRES in the control of c-mycgene expression throughout development, either during embryogenesis where its activity might participate in cell proliferation or later on, where its silencing could contribute to the downregulation of c-myc expression, whose deregulation leads to tumor formation.
机译：c- myc 原癌基因的表达是细胞增殖和凋亡的关键调节因子，在不同的转录水平和转录后水平均受到控制。特别是，c- myc mRNA包含一个内部核糖体进入位点（IRES），能够独立于经典的帽依赖性机制而促进翻译起始。我们分析了c- myc IRES活性在不同增殖细胞类型中的体外变化，以及在体内表达双顺反子双荧光素酶构建体的转基因小鼠体内的变化。在相同条件下，将c- myc IRES的效率与脑心肌炎病毒（EMCV）的IRES进行了比较。 c- myc IRES是活跃的，但在所有瞬时转染的细胞类型中效率都不同。它在11日龄（E11）胚胎和E16胚胎的某些组织中也有活性。令人惊讶的是，在所有测试的成人器官中，其活性均未检测到或非常低。相反，EMCC IRES在离体的大多数细胞类型以及胚胎和成年组织中非常活跃。这些数据表明，IRES在整个发育过程中在控制c- myc 基因表达中起着至关重要的作用，无论是在胚胎发生过程中（其活性可能参与细胞增殖），还是在稍后阶段，其沉默可能有助于下调。 c- myc 表达的表达失调导致肿瘤形成。

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