Vazquez-Pianzola P, Hernández G, Suter B, Rivera-Pomar R
Max-Planck-Institut für biophysikalische Chemie, Abt. Molekulare Biologie, Am Fassberg 11, Göttingen, Germany.
Cell Death Differ. 2007 Feb;14(2):286-95. doi: 10.1038/sj.cdd.4401990. Epub 2006 Jun 23.
Protein synthesis is inhibited during apoptosis. However, the translation of many mRNAs still proceeds driven by internal ribosome entry sites (IRESs). Here we show that the 5'UTR of hid and grim mRNAs promote translation of uncapped-mRNA reporters in cell-free embryonic extracts and that hid and grim mRNA 5'UTRs drive IRES-mediated translation. The translation of capped-reporters proceeds in the presence of cap competitor and in extracts where cap-dependent translation is impaired. We show that the endogenous hid and grim mRNAs are present in polysomes of heat-shocked embryos, indicating that cap recognition is not required for translation. In contrast, sickle mRNA is translated in a cap-dependent manner in all these assays. Our results show that IRES-dependent initiation may play a role in the translation of Drosophila proapoptotic genes and suggest a variety of regulatory pathways.
细胞凋亡过程中蛋白质合成受到抑制。然而,许多mRNA的翻译仍由内部核糖体进入位点(IRES)驱动继续进行。在此我们表明,hid和grim mRNA的5'非翻译区(UTR)可促进无细胞胚胎提取物中无帽mRNA报告基因的翻译,且hid和grim mRNA的5'UTR驱动IRES介导的翻译。在存在帽竞争剂的情况下以及在帽依赖性翻译受损的提取物中,有帽报告基因的翻译仍可进行。我们发现,内源性hid和grim mRNA存在于热休克胚胎的多核糖体中,这表明翻译不需要帽识别。相比之下,在所有这些实验中,镰刀状mRNA是以帽依赖性方式进行翻译的。我们的结果表明,IRES依赖性起始可能在果蝇促凋亡基因的翻译中起作用,并提示了多种调控途径。