Maran A, Maitra R K, Kumar A, Dong B, Xiao W, Li G, Williams B R, Torrence P F, Silverman R H
Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195.
Science. 1994 Aug 5;265(5173):789-92. doi: 10.1126/science.7914032.
Activation of 2-5A-dependent ribonuclease by 5'-phosphorylated, 2',5'-linked oligoadenylates, known as 2-5A, is one pathway of interferon action. Unaided uptake into HeLa cells of 2-5A linked to an antisense oligonucleotide resulted in the selective ablation of messenger RNA for the double-stranded RNA (dsRNA)-dependent protein kinase PKR. Similarly, purified, recombinant human 2-5A-dependent ribonuclease was induced to selectively cleave PKR messenger RNA. Cells depleted of PKR activity were unresponsive to activation of nuclear factor-kappa B (NF-kappa B) by the dsRNA poly(I):poly(C), which provides direct evidence that PKR is a transducer for the dsRNA signaling of NF-kappa B.
由5'-磷酸化的2',5'-连接的寡聚腺苷酸（即2-5A）激活2-5A依赖性核糖核酸酶是干扰素作用的一条途径。与反义寡核苷酸相连的2-5A在未借助其他手段的情况下被摄取到HeLa细胞中，导致双链RNA（dsRNA）依赖性蛋白激酶PKR的信使RNA被选择性消除。同样，纯化的重组人2-5A依赖性核糖核酸酶被诱导选择性切割PKR信使RNA。缺乏PKR活性的细胞对dsRNA多聚肌苷酸:多聚胞苷酸（poly(I):poly(C)）激活核因子κB（NF-κB）无反应，这直接证明PKR是NF-κB的dsRNA信号转导分子。
