Small interfering RNA-induced transcriptional gene silencing in human cells

被引:724
作者
Morris, KV
Chan, SWL
Jacobsen, SE
Looney, DJ
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[4] VA San Diego Healthcare Syst, Infect Dis, San Diego, CA 92161 USA
关键词
D O I
10.1126/science.1101372
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
Small interfering RNA (siRNA) and rnicroRNA silence genes at the transcriptional, posttranscriptional, and/or translational level. Using human tissue culture cells, we show that promoter-directed siRNA inhibits transcription of an integrated, proviral, elongation factor 1 alpha (EF1A) promoter-green fluorescent protein reporter gene and of endogenous EF1A. Silencing was associated with DNA methylation of the targeted sequence, and it required either active transport of siRNA into the nucleus or permeabilization of the nuclear envelope by lentiviral transduction. These results demonstrate that siRNA-directed transcriptional silencing is conserved in mammals, providing a means to inhibit mammalian gene function.
引用
收藏
页码:1289 / 1292
页数:4
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