RNA-DIRECTED CONTROL OF TRANSCRIPTION IN HUMAN CELLS: SPECIFICALLY TURNING GENES ON OR OFF

Abstract

The deregulation of gene expression is found in virtually every malady afflicting humans. From cancer to HIV-1 the uncontrolled expression or loss of gene expression is prevalent. Clearly, the ability to specifically control transcription would prove exceedingly useful with regards to approaches to avert disease. It has been known for several years now that small antisense non-coding RNAs can induce transcriptional gene silencing in humans suggesting that a mechanism is operative whereby non-coding RNAs exert transcriptional control of gene expression. Only recently was it observed 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 modulate transcription. These observations present an interesting paradigm where it is now possible to either stably silence transcription by targeting small antisense non-coding RNAs to particular gene promoters, or modulate increases in transcription by targeting the degradation of the regulatory long antisense non-coding RNA. This review will highlight the mechanism of action whereby antisense non-coding RNAs modulate transcriptional gene silencing as well as discuss the realized potential to therapeutically regulate the expression of virtually any gene, i.e., turn it on or off as desired.