Pyronnet S, Pradayrol L, Sonenberg N
INSERM U531, Institut Louis Bugnard IFR31, BP84225, Hôpital Rangueil, 31432 Toulouse Cedex 4, France.
Cell Mol Life Sci. 2005 Jun;62(11):1267-74. doi: 10.1007/s00018-005-5020-8.
Ornithine decarboxylase (ODC) is the ratelimiting enzyme in the biosynthesis of polyamines, which are required for optimal cell growth and proliferation. ODC is overexpressed in many tumors and, conversely, its overexpression induces transformation. We have previously reported that ODC mRNA alternative splicing relieves the translation repression normally imposed by a long and structured 5' untranslated region (UTR), and that the ODC 5' UTR contains an internal ribosome entry site (IRES). Here we show that ODC IRES activity is enhanced following inclusion of alternative sequences generated by splicing at cryptic acceptor sites. Furthermore, the alternative ODC IRES is more sensitive to cell-cycledependent changes in the rate of translation. These findings uncover a new biological property of differentially spliced transcripts. This is the first example of alternative splicing that modulates mRNA translation through the cell cycle in a cap-independent manner.
鸟氨酸脱羧酶（ODC）是多胺生物合成中的限速酶，而多胺是细胞最佳生长和增殖所必需的。ODC在许多肿瘤中过度表达，相反，其过度表达会诱导细胞转化。我们之前报道过，ODC mRNA的可变剪接可解除通常由长且结构复杂的5'非翻译区（UTR）施加的翻译抑制，并且ODC的5'UTR包含一个内部核糖体进入位点（IRES）。在此我们表明，在包含由隐蔽受体位点剪接产生的可变序列后，ODC IRES活性增强。此外，可变的ODC IRES对翻译速率中细胞周期依赖性变化更敏感。这些发现揭示了差异剪接转录本的一种新生物学特性。这是以不依赖帽子的方式通过细胞周期调节mRNA翻译的可变剪接的首个实例。
