MECHANISM FOR DISCRIMINATION BETWEEN VIRAL AND HOST MESSENGER-RNA IN INTERFERON-TREATED CELLS
MECHANISM FOR DISCRIMINATION BETWEEN VIRAL AND HOST MESSENGER-RNA IN INTERFERON-TREATED CELLS
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DOI：
10.1073/pnas.76.6.2600
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发表时间：
1979-01-01
影响因子：
11.1
通讯作者：
BAGLIONI, C
中科院分区：
文献类型：
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作者：
NILSEN, TW;BAGLIONI, C
在干扰素处理的 [人宫颈癌] HeLa 细胞的提取物中，与未与 dsRNA 连接的 mRNA 相比，与双链 (ds)RNA 共价连接的 RNA 优先被降解。这是通过跟踪与聚（U）退火的含聚（A）的mRNA、与聚（I）退火的含聚（C）的脑心肌炎病毒RNA以及从感染细胞中分离的病毒的复制中间体的降解来确定的。在干扰素处理的细胞提取物中，dsRNA 促进一系列寡核苷酸（称为 (2''-5'')oligo(A)）的合成，进而激活核酸内切酶。多项证据表明 (2''-5'')oligo(A) 聚合酶/核酸内切酶系统参与与 dsRNA 连接的 mRNA 的优先降解。阻止 (2''-5'')oligo(A) 合成的条件可防止这种优先降解，而添加 (2''-5'')oligo(A) 或有利于其合成的条件会导致与 dsRNA 连接和不连接的 mRNA 降解。这些结果可以通过模型底物 dsRNA 区域附近核酸内切酶的局部激活得到最好的解释。在受感染的细胞中，核酸内切酶的激活发生在 RNA 病毒复制中间体附近。脑心肌炎病毒的复制中间体促进干扰素处理细胞提取物中 (2''-5'')oligo(A) 的合成，并降解为抗 RNase A 消化的 20S 核心。这种机制可能是区分干扰素处理细胞中病毒和细胞 mRNA 的原因。
In extracts of interferon-treated [human cervical carcinoma] HeLa cells, RNA covalently linked to double-stranded (ds)RNA is preferentially degraded compared with mRNA not linked to dsRNA. This was established by following the degradation of poly(A)-containing mRNA annealed with poly(U), of poly(C)-containing encephalomyocarditis virus RNA annealed with poly(I), and of the replicative intermediate of the virus isolated from infected cells. In extracts of interferon-treated cells, dsRNA promotes the synthesis of a series of oligonucleotides, designated (2''-5'')oligo(A), which in turn activate an endonuclease. Several lines of evidence suggest that the (2''-5'')oligo(A) polymerase/endonuclease system is involved in the preferential degradation of mRNA linked to dsRNA. Conditions that prevent synthesis of (2''-5'')oligo(A) prevent this preferential degradation, whereas addition of (2''-5'')oligo(A) or conditions that favor its synthesis result in degradation of mRNA both linked and not linked to dsRNA. These results are best explained by a localized activation of the endonuclease near the dsRNA region of the model substrates. In infected cells activation of the endonuclease takes place near the replicative intermediates of RNA viruses. The replicative intermediates of encephalomyocarditis virus promote synthesis of (2''-5'')oligo(A) in extracts of interferon-treated cells and are degraded to a 20S core resistant to digestion with RNase A. This mechanism may be responsible for discrimination between viral and cellular mRNA in interferon-treated cells.