MicroRNA-directed transcriptional gene silencing in mammalian cells

被引：529

作者：

Kim, Daniel H. ^{[1
,2
]}

Saetrom, Pal ^{[3
,4
,5
]}

Snove, Ola ^{[3
,4
]}

Rossi, John J. ^{[1
,2
]}

机构：

[1] Beckman Res Inst City Hope, Grad Sch Biol Sci, Duarte, CA 91010 USA

[2] Beckman Res Inst City Hope, Div Mol Biol, Duarte, CA 91010 USA

[3] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NO-7489 Trondheim, Norway

[4] Interagon AS, Lab Senteret, NO-7489 Trondheim, Norway

[5] Norwegian Univ Sci & Technol, Dept Comp & Informat Sci, NO-7491 Trondheim, Norway

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 42期

基金：

美国国家卫生研究院;

关键词：

miRNA; POLR3D; RNAi; Argonaute; epigenetic;

D O I：

10.1073/pnas.0808830105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：16230 / 16235

页数：6

共 26 条

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