Human interferon-γ mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR

被引：201

作者：

Ben-Asouli, Y ^{[1
]}

Banai, Y ^{[1
]}

Pel-Or, Y ^{[1
]}

Shir, A ^{[1
]}

Kaempfer, R ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91120 Jerusalem, Israel

来源：

CELL | 2002年 / 108卷 / 02期

关键词：

D O I：

10.1016/S0092-8674(02)00616-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

PKR, an interferon (IFN)-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2alpha chain. We show that human IFN-gamma mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-gamma mRNA activates PKR through a pseudoknot in its 5' untranslated region. Mutations that impair pseudoknot stability reduce the ability to activate PKR and strongly increase the translation efficiency of IFN-gamma mRNA. Nonphosphorylatable mutant eIF2alpha, knockout of PKR and PKR inhibitors 2-aminopurine, transdominant-negative PKR, or vaccinia E3L correspondingly enhances translation of IFN-gamma mRNA. The potential to form the pseudoknot is phylogenetically conserved. We propose that the RNA pseudoknot acts to adjust translation of IFN-gamma mRNA to the PKR level expressed in the cell.

引用

页码：221 / 232

页数：12

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