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首页> 外文期刊>Molecular and Cellular Biology >Potential Alu Function: Regulation of the Activity of Double-Stranded RNA-Activated Kinase PKR
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Potential Alu Function: Regulation of the Activity of Double-Stranded RNA-Activated Kinase PKR

机译：潜在的铝功能：调节双链RNA激活激酶PKR的活性。

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摘要

Cell stress, viral infection, and translational inhibition increase the abundance of human Alu RNA, suggesting that the level of these transcripts is sensitive to the translational state of the cell. To determine whether Alu RNA functions in translational homeostasis, we investigated its role in the regulation of double-stranded RNA-activated kinase PKR. We found that overexpression of Alu RNA by cotransient transfection increased the expression of a reporter construct, which is consistent with an inhibitory effect on PKR. Alu RNA formed stable, discrete complexes with PKR in vitro, bound PKR in vivo, and antagonized PKR activation both in vitro and in vivo. Alu RNAs produced by either overexpression or exposure of cells to heat shock bound PKR, whereas transiently overexpressed Alu RNA antagonized virus-induced activation of PKR in vivo. Cycloheximide treatment of cells decreased PKR activity, coincident with an increase in Alu RNA. These observations suggest that the increased levels of Alu RNAs caused by cellular exposure to different stresses regulate protein synthesis by antagonizing PKR activation. This provides a functional role for mammalian short interspersed elements, prototypical junk DNA.
机译：细胞应激，病毒感染和翻译抑制会增加人类Alu RNA的丰度，表明这些转录本的水平对细胞的翻译状态敏感。为了确定Alu RNA是否在翻译动态平衡中起作用，我们调查了其在调节双链RNA激活的激酶PKR中的作用。我们发现通过共瞬时转染而过表达Alu RNA增加了报告基因构建体的表达，这与对PKR的抑制作用一致。 Alu RNA在体外与PKR形成稳定，离散的复合物，在体内与PKR结合，并在体外和体内拮抗PKR活化。通过细胞过度表达或暴露于热休克而产生的Alu RNA与PKR结合，而瞬时过表达的Alu RNA在体内拮抗病毒诱导的PKR激活。环己酰亚胺处理细胞会降低PKR活性，与Alu RNA的增加同时发生。这些观察结果表明，由于细胞暴露于不同的压力而导致的Alu RNA含量升高，可通过拮抗PKR激活来调节蛋白质合成。这为哺乳动物的短穿插元素，典型的垃圾DNA提供了功能性作用。

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