Cencig Sabrina, Nanbru Cécile, Le Shu-Yun, Gueydan Cyril, Huez Georges, Kruys Véronique
Laboratoire de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, rue des Profs Jeener et Brachet 12, 6041 Gosselies, Belgium.
Oncogene. 2004 Jan 8;23(1):267-77. doi: 10.1038/sj.onc.1207017.
The human c-myc proto-oncogene is transcribed from four alternative promoters generating transcripts with 5' untranslated regions of various lengths. These transcripts encode two proteins, c-Myc1 and c-Myc2, from two initiation codons, CUG and AUG, respectively. We and others have previously demonstrated that the region of c-myc transcripts between nucleotides (nt) -363 and -94 upstream from the CUG start codon contained an internal ribosome entry site leading to the cap-independent translation of c-myc open reading frames (ORFs). Here, we mapped a 50-nt sequence (-143 -94), which is sufficient to promote internal translation initiation of c-myc ORFs. Interestingly, this 50-nt element can be further dissected into two segments of 14 nt, each capable of activating internal translation initiation. We also demonstrate that this 50-nt element acts as the ribosome landing site from which the preinitiation ribosomal complex scans the mRNA until the CUG or AUG start codons.
人类c-myc原癌基因由四个可变启动子转录，产生具有不同长度5'非翻译区的转录本。这些转录本分别从两个起始密码子CUG和AUG编码两种蛋白质，即c-Myc1和c-Myc2。我们和其他人之前已经证明，在CUG起始密码子上游核苷酸（nt）-363至-94之间的c-myc转录本区域包含一个内部核糖体进入位点，导致c-myc开放阅读框（ORF）的不依赖帽的翻译。在这里，我们绘制了一个50 nt的序列（-143至-94），该序列足以促进c-myc ORF的内部翻译起始。有趣的是，这个50 nt的元件可以进一步细分为两个14 nt的片段，每个片段都能够激活内部翻译起始。我们还证明，这个50 nt的元件充当核糖体着陆位点，起始前核糖体复合物从该位点扫描mRNA，直到CUG或AUG起始密码子。
