Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells

作者：Kevin V. Morris, Wan Chan, Steven E. Jacobsen, David J. Looney · 发表于：Science · 年份：2004 · DOI：10.1126/science.1101372 · 被引用次数：929 · 研究领域：RNA Interference and Gene Delivery、RNA Research and Splicing、MicroRNA in disease regulation

Small interfering RNA (siRNA) and microRNA 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 1alpha (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.