Translational control of the interferon regulatory factor 2 mRNA by IRES element.
Translational control of the interferon regulatory factor 2 mRNA by IRES element.
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DOI：
10.1093/nar/gkm524
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发表时间：
2007
影响因子：
14.9
通讯作者：
Das, Saumitra
中科院分区：
文献类型：
--
作者：
Dhar, Debojyoti;Roy, Swagata;Das, Saumitra
翻译控制代表了胁迫条件下基因表达的重要调控模式。我们研究了干扰素调节因子2（interferonregulationfactor 2，IRF 2）mRNA的翻译，证实了IRF 2 RNA的5′UTR存在内部核糖体进入位点（internalribosomeentry site，IRES）元件。各种对照实验排除了IRF 2 RNA内部起始中的漏扫描、隐蔽启动子活性或RNA剪接的贡献。似乎IRF 2-IRES功能对eIF 4G切割不敏感，因为其活性在柯萨奇病毒2A蛋白酶存在下仅受到轻微影响。干扰素α处理对IRF 2-IRES活性和蛋白水平无明显影响。此外，在用衣霉素（一种引起内质网（ER）应激的药物）处理的细胞中，IRF 2-IRES活性和蛋白水平不受影响，尽管帽依赖性翻译严重受损。与IRF 2-IRES结合的细胞蛋白的分析表明某些细胞因子可能在应激条件下影响其功能。有趣的是，PTB蛋白的部分敲低显著抑制IRF 2-IRES功能。两者合计，似乎IRF 2基因在应激条件下的表达是由IRES元件控制的，这反过来又影响细胞反应。
Translational control represents an important mode of regulation of gene expression under stress conditions. We have studied the translation of interferon regulatory factor 2 (IRF2) mRNA, a negative regulator of transcription of interferon-stimulated genes and demonstrated the presence of internal ribosome entry site (IRES) element in the 5′UTR of IRF2 RNA. Various control experiments ruled out the contribution of leaky scanning, cryptic promoter activity or RNA splicing in the internal initiation of IRF2 RNA. It seems IRF2-IRES function is not sensitive to eIF4G cleavage, since its activity was only marginally affected in presence of Coxsackievirus 2A protease. Interferon α treatment did not affect the IRF2-IRES activity or the protein level significantly. Also, in cells treated with tunicamycin [an agent causing endoplasmic reticulum (ER) stress], the IRF2-IRES activity and the protein levels were unaffected, although the cap-dependent translation was severely impaired. Analysis of the cellular protein binding with the IRF2-IRES suggests certain cellular factors, which might influence its function under stress conditions. Interestingly, partial knockdown of PTB protein significantly inhibited the IRF2-IRES function. Taken together, it appears that IRF2 gene expression during stress condition is controlled by the IRES element, which in turn influences the cellular response.