Bernstein J, Sella O, Le S Y, Elroy-Stein O
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
J Biol Chem. 1997 Apr 4;272(14):9356-62. doi: 10.1074/jbc.272.14.9356.
It has become clear that a given cell type can qualitatively and quantitatively affect the expression of the platelet-derived growth factor B (PDGF2/c-sis) gene at multiple levels. In a previous report, we showed that PDGF2/c-sis 5'-untranslated region has a translational modulating activity during megakaryocytic differentiation of K562 cells. This study points to the mechanism used for this translational modulation. The unusual mRNA leader, which imposes a major barrier to conventional ribosomal scanning, was found to contain an internal ribosomal entry site that becomes more potent in differentiating cells and was termed differentiation-linked internal ribosomal entry site (D-IRES). The D-IRES element defines a functional role for the cumbersome 1022-nucleotide-long mRNA leader and accounts for its uncommon, evolutionary conserved architecture. The differentiation-linked enhancement of internal translation, which provides an additional step to the fine tuning of PDGF2/c-sis gene expression, might be employed by numerous critical regulatory genes with unusual mRNA leaders and might have widespread implications for cellular growth and development.
已经清楚的是，特定的细胞类型能够在多个水平上定性和定量地影响血小板衍生生长因子B（PDGF2/c-sis）基因的表达。在先前的一份报告中，我们表明PDGF2/c-sis 5'非翻译区在K562细胞的巨核细胞分化过程中具有翻译调节活性。本研究指出了这种翻译调节所使用的机制。发现这个对传统核糖体扫描构成主要障碍的异常mRNA前导序列含有一个内部核糖体进入位点，该位点在分化细胞中变得更有效，并被称为分化相关内部核糖体进入位点（D-IRES）。D-IRES元件确定了这个冗长的1022个核苷酸长的mRNA前导序列的功能作用，并解释了其不寻常的、进化保守的结构。内部翻译的分化相关增强为PDGF2/c-sis基因表达的微调提供了额外的一步，可能被许多具有异常mRNA前导序列的关键调节基因所采用，并且可能对细胞生长和发育具有广泛的影响。
