Involvement of AGO1 and AGO2 in mammalian transcriptional silencing
Involvement of AGO1 and AGO2 in mammalian transcriptional silencing
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DOI：
10.1038/nsmb1140
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发表时间：
2006-09-01
影响因子：
16.8
通讯作者：
Corey, David R.
中科院分区：
文献类型：
--
作者：
Janowski, Bethany A.;Huffman, Kenneth E.;Corey, David R.
与信使RNA互补的双链RNA通过RNA干扰(RNAi)抑制哺乳动物细胞中的翻译。已有研究报道，与启动子DNA互补的RNA也能抑制基因表达。在这里，我们证明了人类ArgAerte-1(AGO1)和ArgAerte-2(AGO2)的同源物将靶向mRNA的沉默通路与介导DNA识别的通路联系在一起。我们发现，与基因启动子的转录起始点或更多上游区域互补的合成抗基因RNA(AgRNAs)抑制了基因的转录。这种沉默发生在细胞核内，需要高启动子活性，并不一定需要组蛋白修饰。在用agRNAs处理的细胞中，AGO1和AGO2与启动子DNA相关，抑制AGO1或AGO2的表达可以逆转转录和转录后沉默。我们的数据表明在哺乳动物细胞中转录和转录后沉默途径之间的关键联系和重要的机制差异。
Duplex RNAs complementary to messenger RNA inhibit translation in mammalian cells by RNA interference (RNAi). Studies have reported that RNAs complementary to promoter DNA also inhibit gene expression. Here we show that the human homologs of Argonaute-1 (AGO1) and Argonaute-2 (AGO2) link the silencing pathways that target mRNA with pathways mediating recognition of DNA. We find that synthetic antigene RNAs (agRNAs) complementary to transcription start sites or more upstream regions of gene promoters inhibit gene transcription. This silencing occurs in the nucleus, requires high promoter activity and does not necessarily require histone modification. AGO1 and AGO2 associate with promoter DNA in cells treated with agRNAs, and inhibiting expression of AGO1 or AGO2 reverses transcriptional and post-transcriptional silencing. Our data indicate key linkages and important mechanistic distinctions between transcriptional and post-transcriptional silencing pathways in mammalian cells.