Protein kinase R contributes to immunity against specific viruses by regulating interferon mRNA integrity.
Protein kinase R contributes to immunity against specific viruses by regulating interferon mRNA integrity.
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DOI：
10.1016/j.chom.2010.04.007
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发表时间：
2010-05-20
影响因子：
30.3
通讯作者：
Reis e Sousa C
中科院分区：
文献类型：
--
作者：
Schulz O;Pichlmair A;Rehwinkel J;Rogers NC;Scheuner D;Kato H;Takeuchi O;Akira S;Kaufman RJ;Reis e Sousa C
RNA解旋酶RIG-I和MDA 5对病毒RNA的胞质识别被认为是RNA病毒诱导IFN-α/β的主要途径。然而，其他细胞质RNA传感器在历史上与IFN-α/β产生有关。在这里，我们重新研究了双链RNA结合蛋白激酶R（PKR）的作用。使用表达非功能性PKR或激酶水平降低的细胞，我们表明PKR是产生IFN-α/β蛋白所需的，以响应RNA病毒的子集，包括脑心肌炎，Theiler小鼠脑脊髓炎和Semliki森林病毒，但不是流感或仙台病毒。令人惊讶的是，IFN-α/β mRNA的诱导在PKR缺陷细胞中基本正常。然而，大部分mRNA缺乏poly A尾，表明其完整性受到损害。我们的研究结果表明，PKR在IFN-α/β的产生中起着非冗余的作用，部分是通过调节IFN-α/β mRNA的稳定性来响应一些但不是所有的病毒。
Cytosolic recognition of viral RNA by the RNA helicases RIG-I and MDA5 is thought to be the major pathway for IFN-α/β induction by RNA viruses. However, other cytoplasmic RNA sensors have historically been implicated in IFN-α/β production. Here we have re-examined the role of the double-stranded RNA binding protein kinase R (PKR). Using cells expressing non-functional PKR or reduced levels of kinase, we show that PKR is required for production of IFN-α/β proteins in response to a subset of RNA viruses including encephalomyocarditis, Theiler’s murine encephalomyelitis and Semliki Forest virus but not influenza or Sendai virus. Surprisingly, induction of IFN-α/β mRNA is largely normal in PKR-deficient cells. However, much of that mRNA lacks the poly A tail, indicating that its integrity is compromised. Our results suggest that PKR plays a non-redundant role in IFN-α/β production in response to some but not all viruses, in part by regulating IFN-α/β mRNA stability.
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影响因子：
56.9
作者：
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.
通讯作者：
Sousa, Caetano Reis E.
影响因子：
6.2
作者：
Carpentier, Pamela A.;Williams, Bryan R.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
影响因子：
5.4
作者：
Gilfoy, Felicia D.;Mason, Peter W.
通讯作者：
Mason, Peter W.
DOI：
10.1046/j.1432-1033.2003.03530.x
发表时间：
2003-04-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Pasté, M;Huez, G;Kruys, V
通讯作者：
Kruys, V
影响因子：
4.8
作者：
McAllister, Christopher S.;Samuel, Charles E.
通讯作者：
Samuel, Charles E.