The AU-rich sequences in the 3' untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids.
The AU-rich sequences in the 3' untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids.
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DOI：
10.1084/jem.173.2.349
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发表时间：
1991-02-01
期刊：
影响因子：
--
通讯作者：
Baglioni C
中科院分区：
文献类型：
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作者：
Peppel K;Vinci JM;Baglioni C
构建了组成型表达人干扰素-β（IFN-β）mRNA并在3'非翻译区（UTR）中含有各种缺失的不同载体。在两个载体中特异性缺失3' UTR中的富含AU的序列。通过用载体转染小鼠L929细胞建立分泌人IFN-β的细胞系。这些细胞显示出相似的IFN-β mRNA水平，并分泌相当量的IFN-β，表明富含AU的序列的缺失对该mRNA的稳定性没有影响，并且对该mRNA的翻译效率几乎没有影响。合成的糖皮质激素地塞米松先前被证明可以增加IFN-β mRNA的周转。地塞米松的这种活性仅在表达IFN-β mRNA的细胞中清楚地观察到，所述IFN-β mRNA在3' UTR中具有富含AU的序列。在放线菌酮的存在下，这种mRNA的周转率增加;因此，它不需要合成新的蛋白质。这些发现表明糖皮质激素可以激活核糖核酸酶，其降解在3' UTR中含有富含AU序列的mRNA。
Different vectors were constructed that expressed the human interferon- beta (IFN-beta) mRNA constitutively and contained various deletions in the 3' untranslated region (UTR). AU-rich sequences in the 3' UTR were specifically deleted in two vectors. Cell lines secreting human IFN- beta were established by transfecting murine L929 cells with the vectors. These cells showed similar levels of IFN-beta mRNA and secreted comparable amounts of IFN-beta, indicating that the deletion of AU-rich sequences had no effect on the stability and little effect on the efficiency of translation of this mRNA. The synthetic glucocorticoid dexamethasone was previously shown to increase the turnover of IFN-beta mRNA. This activity of dexamethasone was clearly observed only in cells expressing IFN-beta mRNA with AU-rich sequences in the 3' UTR. The increased turnover of this mRNA occurred in the presence of cycloheximide; therefore, it did not require synthesis of new proteins. These findings suggest that glucocorticoids may activate a ribonuclease that degrades mRNAs containing AU-rich sequences in the 3' UTR.