Pedersen Susanne K, Christiansen Jan, Hansen Thomas v O, Larsen Martin R, Nielsen Finn C
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Biochem J. 2002 Apr 1;363(Pt 1):37-44. doi: 10.1042/0264-6021:3630037.
Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IGF-II leader 3 mRNA translation is regulated by a rapamycin-sensitive pathway, whereas leader 4 mRNA is constitutively translated, but so far the significance of leader 2 mRNA has been unclear. Here, we show that leader 2 mRNA is translated efficiently in an eIF4E-independent manner. In a bicistronic vector system, the 411 nt leader 2 was capable of internal initiation via a phylogenetically conserved internal ribosome entry site (IRES), located in the 3' half of the leader. The IRES is composed of an approx. 120 nt ribosome recruitment element, followed by an 80 nt spacer region, which is scanned by the ribosomal pre-initiation complex. Since cap-dependent translation is down-regulated during cell division, leader 2 might facilitate a continuous IGF-II production in rapidly dividing cells during development.
胰岛素样生长因子II（IGF-II）是一种胎儿生长因子，属于胰岛素样肽家族。在胎儿期，IGF-II基因产生三种具有不同5'非翻译区（UTR）但编码区和3'UTR相同的mRNA。我们之前已经表明，IGF-II前导序列3 mRNA的翻译受雷帕霉素敏感途径调控，而前导序列4 mRNA组成性翻译，但到目前为止，前导序列2 mRNA的意义尚不清楚。在这里，我们表明前导序列2 mRNA以不依赖eIF4E的方式有效翻译。在双顺反子载体系统中，411 nt的前导序列2能够通过位于前导序列3'半部分的系统发育保守的内部核糖体进入位点（IRES）进行内部起始。该IRES由一个约120 nt的核糖体募集元件组成，后面跟着一个80 nt的间隔区，核糖体预起始复合物会扫描该间隔区。由于在细胞分裂过程中帽依赖性翻译被下调，前导序列2可能有助于在发育过程中快速分裂的细胞中持续产生IGF-II。
