人类c-myc P0三顺反子mRNA的翻译涉及两个独立的内部核糖体进入位点。

Translation of the human c-myc P0 tricistronic mRNA involves two independent internal ribosome entry sites.

作者信息

Nanbru C, Prats A C, Droogmans L, Defrance P, Huez G, Kruys V

机构信息

Laboratoire de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, rue Profs Jeener et Brachet 12, 6041 Gosselies, Belgium.

出版信息

Oncogene. 2001 Jul 12;20(31):4270-80. doi: 10.1038/sj.onc.1204548.

DOI:10.1038/sj.onc.1204548

PMID:11464293

Abstract

The human c-myc proto-oncogene is transcribed from four alternative promoters (P0, P1, P2, and P3) giving rise to mRNAs having 5' leader sequences of various length. The c-myc P0 mRNA contains three open reading frames (ORFs), the last one encoding c-Myc1 and c-Myc2 proteins generated by alternative translation initiated at CUG and AUG codons. The middle ORF (MYCHEX1) and the 5' ORF (ORF1) code for proteins 188 and 114 amino acids in length, respectively. We and others previously identified an internal ribosome entry site (IRES) in P0 and P2 c-myc mRNAs, promoting the cap-independent translation of c-Myc1 and c-Myc2. Here, we report the presence of a second IRES (named IRES1) promoting the cap-independent translation of MYCHEX1 in c-myc P0 mRNA. Using deletion analysis, we mapped an 80-nt region essential for IRES1 activity. c-myc P0 mRNA is thus the first eukaryotic polycistronic mRNA described for which translation initiation of two different open reading frames (MYCHEX1 and c-Myc1/c-Myc2) involves internal ribosome entry.

摘要

人类c-myc原癌基因由四个可变启动子（P0、P1、P2和P3）转录，产生具有不同长度5'前导序列的mRNA。c-myc P0 mRNA包含三个开放阅读框（ORF），最后一个编码由在CUG和AUG密码子处起始的可变翻译产生的c-Myc1和c-Myc2蛋白。中间的ORF（MYCHEX1）和5'端的ORF（ORF1）分别编码长度为188和114个氨基酸的蛋白质。我们和其他人之前在P0和P2 c-myc mRNA中鉴定出一个内部核糖体进入位点（IRES），促进c-Myc1和c-Myc2的不依赖帽的翻译。在这里，我们报告在c-myc P0 mRNA中存在第二个IRES（命名为IRES1），促进MYCHEX1的不依赖帽的翻译。通过缺失分析，我们确定了一个对IRES1活性至关重要的80个核苷酸区域。因此，c-myc P0 mRNA是描述的第一个真核多顺反子mRNA，其两个不同开放阅读框（MYCHEX1和c-Myc1/c-Myc2）的翻译起始涉及内部核糖体进入。