MicroRNA-directed transcriptional gene silencing in mammalian cells
MicroRNA-directed transcriptional gene silencing in mammalian cells
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DOI：
10.1073/pnas.0808830105
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发表时间：
2008-10-21
影响因子：
11.1
通讯作者：
Rossi, John J.
中科院分区：
文献类型：
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作者：
Kim, Daniel H.;Saetrom, Pal;Rossi, John J.
微小RNA（miRNAs）在细胞质中在转录后水平调节基因表达，但最近的研究结果表明miRNAs在细胞核中的其他作用。为了解决miRNA是否可能在转录上沉默基因表达，我们在人类基因组中搜索了与已知基因转录起始位点邻近的miRNA靶位点。一种保守的miRNA，miR-320，以反义方向编码在细胞周期基因POLR 3D的启动子区域内。我们提供了miR-320在POLR 3D表达的转录沉默中的顺式调节作用的证据。miR-320指导RNA干扰（RNAi）蛋白Argonaute-1（AGO 1）、Polycomb group（PcG）组分EZH 2和三甲基组蛋白H3赖氨酸27（H3 K27 me 3）与POLR 3D启动子的结合。我们的研究结果表明，在哺乳动物细胞中存在一种miRNA指导的转录基因沉默（TGS）的表观遗传机制。
MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level in the cytoplasm, but recent findings suggest additional roles for miRNAs in the nucleus. To address whether miRNAs might transcriptionally silence gene expression, we searched for miRNA target sites proximal to known gene transcription start sites in the human genome. One conserved miRNA, miR-320, is encoded within the promoter region of the cell cycle gene POLR3D in the antisense orientation. We provide evidence of a cis-regulatory role for miR-320 in transcriptional silencing of POLR3D expression. miR-320 directs the association of RNA interference (RNAi) protein Argonaute-1 (AGO1), Polycomb group (PcG) component EZH2, and tri-methyl histone H3 lysine 27 (H3K27me3) with the POLR3D promoter. Our results suggest the existence of an epigenetic mechanism of miRNA-directed transcriptional gene silencing (TGS) in mammalian cells.