De Benedetti A, Baglioni C
Nature. 1984;311(5981):79-81. doi: 10.1038/311079a0.
The initiation of protein synthesis can be regulated in mammalian cells by protein kinases which phosphorylate the alpha subunit of initiation factor eIF-2. This phosphorylation results in a block in the recycling of eIF-2 and in the inhibition of messenger RNA binding to 80S initiation complexes. After eIF-2 alpha is phosphorylated, the mRNA becomes associated with 48S complexes consisting of a 40S ribosomal subunit, eIF-2 (alpha P), GDP and Met-tRNAf. One of the eIF-2 alpha kinases is activated by low concentrations of double-stranded RNA (dsRNA). This kinase (PKds) is present at a basal level in all mammalian cells investigated and its synthesis is induced in cells treated with interferon. The PKds may be involved in the inhibition of translation of viral mRNA in interferon-treated cells infected with RNA viruses, as it is activated by viral replicative complexes. It is not known, however, if the activated PKds preferentially inhibits the translation of viral mRNA when cellular protein synthesis proceeds at a normal rate in infected cells. We now report that mRNA covalently linked to dsRNA is preferentially inhibited from binding to 80S complexes by a localized activation of PKds. This suggests that in interferon-treated cells the binding of some nascent viral mRNAs to functional initiation complexes may be preferentially inhibited by a similar mechanism.
在哺乳动物细胞中，蛋白质合成的起始可由蛋白激酶进行调控，这些激酶使起始因子eIF-2的α亚基磷酸化。这种磷酸化导致eIF-2的循环受阻，并抑制信使核糖核酸与80S起始复合物的结合。eIF-2α磷酸化后，信使核糖核酸与由40S核糖体亚基、eIF-2（αP）、GDP和甲硫氨酰 - tRNAf组成的48S复合物结合。其中一种eIF-2α激酶可被低浓度的双链核糖核酸（dsRNA）激活。这种激酶（PKds）在所研究的所有哺乳动物细胞中均以基础水平存在，其合成在经干扰素处理的细胞中被诱导。PKds可能参与了在感染RNA病毒且经干扰素处理的细胞中对病毒信使核糖核酸翻译的抑制，因为它可被病毒复制复合物激活。然而，尚不清楚当感染细胞中的细胞蛋白质合成以正常速率进行时，被激活的PKds是否优先抑制病毒信使核糖核酸的翻译。我们现在报告，与dsRNA共价连接的信使核糖核酸会因PKds的局部激活而优先被抑制与80S复合物结合。这表明在经干扰素处理的细胞中，一些新生病毒信使核糖核酸与功能性起始复合物的结合可能会通过类似机制被优先抑制。
