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Updated: Jun 18, 2026
DNA Vector-based RNA Interference to Study Gene Function in Cancer
Published on: June 4, 2012
RNA-directed transcriptional gene silencing and activation in human cells
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. kmorris@scripps.edu
Abstract:
The overt loss or uncontrolled gain of gene expression is found at some level in virtually every malady afflicting humans. From cancer to HIV-1, the uncontrolled expression or loss of gene expression is prevalent in human diseases. Approaches toward the specific control of gene expression at the transcriptional level could have the potential to revert or reduce disease pathologies. Over the last several years, researchers have developed methodologies that utilize small antisense non-coding RNAs to specifically silence transcription. Only recently has the endogenous molecular pathway usurped by the introduction of these small RNAs to regulate transcription in human cells been defined. Observations suggest that long antisense non-coding RNAs function as the endogenous epigenetic regulators of transcription in human cells, thus explaining why small antisense RNAs were observed early on to silence transcription via directed epigenetic changes at the target loci. The mechanism of action whereby small regulatory RNAs can either turn gene transcription on or off will be discussed as evidence that one day it may be possible to develop therapeutics to regulate gene transcription and ameliorate particular disease conditions.
Insights
Gene expression dysregulation causes human diseases. Researchers are exploring small antisense non-coding RNAs to control transcription, potentially leading to new gene therapy treatments.
Area of Science:
- Molecular Biology
- Epigenetics
- Human Genetics
Background:
- Gene expression dysregulation, including loss or uncontrolled gain, is implicated in numerous human diseases such as cancer and HIV-1.
- Transcriptional control offers a potential therapeutic strategy to mitigate disease pathologies.
- Small antisense non-coding RNAs have emerged as tools for targeted gene silencing.
Purpose of the Study:
- To define the endogenous molecular pathway utilized by small RNAs for transcriptional regulation in human cells.
- To elucidate the role of long antisense non-coding RNAs as endogenous epigenetic regulators.
- To discuss the mechanism of action for small regulatory RNAs in controlling gene transcription.
Main Methods:
- Investigating the endogenous pathway for small RNA-mediated transcriptional regulation.
- Analyzing the function of long antisense non-coding RNAs in epigenetic gene control.
- Examining the mechanisms by which small RNAs modulate transcription (both activation and repression).
Main Results:
- The endogenous pathway for small RNA-directed transcriptional regulation in human cells has been identified.
- Long antisense non-coding RNAs are proposed as the endogenous epigenetic regulators of transcription.
- Small regulatory RNAs can reversibly control gene transcription, acting as either silencers or activators.
Conclusions:
- Understanding the endogenous mechanisms of gene regulation by non-coding RNAs is crucial.
- Small antisense RNAs can hijack endogenous pathways to modify gene expression.
- These findings pave the way for developing novel therapeutics targeting gene transcription for disease treatment.
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