Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation.
Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation.
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DOI：
10.1093/nar/gkq347
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发表时间：
2010-09
影响因子：
14.9
通讯作者：
Karikó K
中科院分区：
文献类型：
--
作者：
Anderson BR;Muramatsu H;Nallagatla SR;Bevilacqua PC;Sansing LH;Weissman D;Karikó K
以前的研究表明，在体外转录的信使RNA（mRNA）的翻译水平增强时，其尿苷被替换为假尿苷，然而，这种增强的原因尚未确定。在这里，我们证明，在体外转录含有尿苷激活RNA依赖性蛋白激酶（PKR），然后磷酸化翻译起始因子2-α（eIF-2α），并抑制翻译。相反，在体外转录的mRNA含有假尿苷激活PKR的程度较低，和翻译的假尿苷含有mRNA不受抑制。RNA下拉分析表明，含有尿苷的mRNA比含有假尿苷的mRNA更有效地被PKR结合。最后，PKR的作用是通过显示假尿苷和尿苷的RNA在PKR敲除细胞中被同等地翻译来验证的。这些结果表明，与含有尿苷的mRNA相比，含有假尿苷的mRNA的翻译增强是由PKR活化降低介导的。
Previous studies have shown that the translation level of in vitro transcribed messenger RNA (mRNA) is enhanced when its uridines are replaced with pseudouridines; however, the reason for this enhancement has not been identified. Here, we demonstrate that in vitro transcripts containing uridine activate RNA-dependent protein kinase (PKR), which then phosphorylates translation initiation factor 2-alpha (eIF-2α), and inhibits translation. In contrast, in vitro transcribed mRNAs containing pseudouridine activate PKR to a lesser degree, and translation of pseudouridine-containing mRNAs is not repressed. RNA pull-down assays demonstrate that mRNA containing uridine is bound by PKR more efficiently than mRNA with pseudouridine. Finally, the role of PKR is validated by showing that pseudouridine- and uridine-containing RNAs were translated equally in PKR knockout cells. These results indicate that the enhanced translation of mRNAs containing pseudouridine, compared to those containing uridine, is mediated by decreased activation of PKR.
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影响因子：
6.7
作者：
Dauber B;Martínez-Sobrido L;Schneider J;Hai R;Waibler Z;Kalinke U;García-Sastre A;Wolff T
通讯作者：
Wolff T
影响因子：
12.4
作者：
Kariko, Katalin;Muramatsu, Hiromi;Welsh, Frank A.;Ludwig, Janos;Kato, Hiroki;Akira, Shizuo;Weissman, Drew
通讯作者：
Weissman, Drew
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作者：
Gorina, Roser;Santalucia, Tomas;Planas, Anna M.
通讯作者：
Planas, Anna M.
影响因子：
2.9
作者：
Bevilacqua, PC;George, CX;Cech, TR
通讯作者：
Cech, TR