Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells

  title={Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells},
  author={Kevin V. Morris and Simon W.-L. Chan and Steven E. Jacobsen and David J. Looney},
  pages={1289 - 1292}
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… 

RNA-mediated transcriptional gene silencing in human cells.

  • K. Morris
  • Biology
    Current topics in microbiology and immunology
  • 2008
The observation that siRNA-directed TGS is operative via epigenetic modifications suggests that similar to plants, and S. Pombe, human genes may also be able to be silenced more permanently or for longer periods following a single treatment and may offer a new therapeutic avenue that could prove robust and of immeasurable therapeutic value in the directed control of target gene expression.

RNA duplexes in transcriptional regulation

RNA-mediated TGS within the NF-κB motif of the human immunodeficiency virus type 1 5′ long tandem repeat promoter region and the associated epigenetic modifications are discussed.

Specific and potent RNAi in the nucleus of human cells

The results provide the first evidence that human RISCs programmed with siRNA are present in the nucleus and can knock down target RNA levels, and reveal new roles for the RNAi machinery in modulating post-transcriptional gene expression inThe nucleus.

siRNAs targeting a chromatin-associated RNA induce its transcriptional silencing in human cells

It is demonstrated that siRNAs targeting a chromatin-associated RNA at distance from its promoter induce its transcriptional silencing, extending the possible repertoire of endogenous or exogenous interfering RNAs.

Stable suppression of gene expression by short interfering RNAs targeted to promoter in a mouse embryonal carcinoma stem cell line

The data presented here indicated long-lasting inhibition in expression of eGFP and puromycin genes, both under the control of the murine Pgk-1 promoter, however, Southern blot analysis showed no methylation in pgk- 1 promoter.

Involvement of AGO1 and AGO2 in mammalian transcriptional silencing

It is found that synthetic antigene RNAs (agRNAs) complementary to transcription start sites or more upstream regions of gene promoters inhibit gene transcription, which occurs in the nucleus, requires high promoter activity and does not necessarily require histone modification.

Small dsRNAs induce transcriptional activation in human cells

A more diverse role for small RNA molecules in the regulation of gene expression than previously recognized is revealed and a potential therapeutic use for dsRNA in targeted gene activation is identified.

Transcriptional regulation by promoter targeted RNAs.

Linkage of small RNA mediated gene regulation and induction of epigenetic regulation in the promoter region in mammals is described.

Testing the putative effect of Dicer-substrate siRNAs in regulating gene expression at transcriptional level

It is concluded that the D-siRNA-induced suppression is likely to occur aft er transcription, and this study tested the hypothesis that Dicer-substrate siRNAs (D-siRNAs), which trigger gene silencing through intrinsic RNAi pathway and are therefore more potent in gene knockdown than traditionally used 21-23mer si RNAs, may also display regulatory eff ects at the transcriptional level.



Hairpin RNAs and Retrotransposon LTRs Effect RNAi and Chromatin-Based Gene Silencing

These analyses directly implicate interspersed LTRs in regulating gene expression during cellular differentiation in plants through nearby retrotransposon long terminal repeats.

RNA: Guiding Gene Silencing

In diverse organisms, small RNAs derived from cleavage of double-stranded RNA can trigger epigenetic gene silencing in the cytoplasm and at the genome level and could play an important role in plant and animal development.

Transcriptional silencing and promoter methylation triggered by double‐stranded RNA

It is shown here that transcriptional gene silencing accompanied by de novo methylation of a target promoter in plants can be triggered by a double‐stranded RNA containing promoter sequences.

The genetics of RNA silencing.

This chapter gives an overview of both biochemical and genetic approaches leading to the current understanding of the molecular mechanism of RNA silencing and its probable biological function.

Nuclear Export of MicroRNA Precursors

Exposure of Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and its depletion by RNA interference results in reduced miRNA levels.

Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs.

It is demonstrated that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5, an additional cellular cofactor required for miRNA biogenesis and function.

Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi

It is proposed that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi.