The 5' untranslated sequence of the c-sis/platelet-derived growth factor 2 transcript is a potent translational inhibitor-猫眼课题宝

c-sis/血小板衍生生长因子 2 转录物的 5 非翻译序列是一种有效的翻译抑制剂

DOI：

发表时间：

1988

期刊：

Molecular and Cellular Biology

影响因子：

5.3

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

C. Rao;M. Pech;K. Robbins;S. Aaronson

c-sis/血小板衍生生长因子2（PDGF-2）是具有转化潜能的原型生长因子。c-sis/PDGF-2转录物含有一个长的5'非翻译序列（UTS），该序列高度富含G. C。为了研究该序列对sis/PDGF-2表达的影响，我们定位了c-sis/PDGF-2启动子，并使用该启动子或猿猴病毒40早期启动子来驱动细菌氯霉素乙酰转移酶或sis/PDGF-2基因的表达。c-sis/PDGF-2 mRNA的5' UTS对RNA表达没有影响，但显示对翻译产生有效的抑制作用。通过缺失分析，我们证明了5' UTS抑制蛋白表达多达40倍。抑制作用是独立的报告基因，细胞类型，或使用的启动子。紧接着c-sis/PDGF-2起始密码子之前的高度富含G. C的140个碱基对序列显示在翻译抑制中几乎与整个5' UTS一样有效。转染分析表明，5' UTS也显著降低sis/PDGF-2基因的转化效率。因此，我们的研究结果提出了一种可能性，即在sis/PDGF-2翻译水平上调节的变化可能在肿瘤表型的发展中发挥作用。

c-sis/platelet-derived growth factor 2 (PDGF-2) is a prototype growth factor with transforming potential. The c-sis/PDGF-2 transcript contains a long 5' untranslated sequence (UTS) that is highly G.C rich. To examine the influence of this sequence on sis/PDGF-2 expression, we localized the c-sis/PDGF-2 promoter and used this promoter or the simian virus 40 early promoter to drive expression of the bacterial chloramphenicol acetyltransferase or sis/PDGF-2 gene. The 5' UTS of c-sis/PDGF-2 mRNA had no effect on RNA expression but was shown to exert a potent inhibitory effect on translation. By deletion analysis, we demonstrated that the 5' UTS inhibited protein expression by as much as 40-fold. The inhibitory effect was independent of reporter gene, cell type, or promoter used. A highly G.C-rich 140-base-pair sequence immediately preceding the c-sis/PDGF-2 initiation codon was shown to be nearly as effective as the entire 5' UTS in translational inhibition. Transfection analysis demonstrated that the 5' UTS significantly reduced the transforming efficiency of the sis/PDGF-2 gene as well. Thus, our findings raise the possibility that changes in regulation at the level of sis/PDGF-2 translation may play a role in development of the neoplastic phenotype.

A method to detect and characterize point mutations in transcribed genes: amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells.