RNA activation: A diamond in the rough for genome engineers

Abstract

The ability to develop efficient and versatile technologies for manipulating gene expression is a fundamental issue both in biotechnology and therapeutics. The endogenous RNA interference (RNAi) pathway which mediates gene silencing was discovered at the end of the 20th century and it is nowadays considered as an essential strategy for knockdown of specific genes and for studying gene function. Remarkably, during the past decade, a RNA-induced mechanism of gene activation has also been reported. Likewise RNAi, the RNA activation (RNAa) process is also mediated by sequence-specific double-stranded RNA (dsRNA) molecules, and interesting resemblances between both RNA-based transcriptional mechanisms have been described. Small activating RNAs (saRNAs) and related molecules have been used for targeting of genes in species that are as different as nematodes and humans, and similar dsRNA-induced activation phenomena have also been observed in plants. The aim of this letter is to highlight recent molecular insights into yet unexplored RNAa mechanism and its potential for manipulating transcriptional activity.