The ability to manipulate gene expression is invaluable for understanding the molecular pathogenesis of disease as well as for developing novel therapeutics. RNA interference provides a robust platform for the knockdown of a specific gene at the post-transcriptional level, but activation of specific genes traditionally has been limited to ligand-mediated activation of signal transduction pathways or introduction of exogenous transgenes from expression vectors. Recent work has shown that small RNA molecules targeted to the promoter region of a gene can activate gene expression. This phenomenon, called RNA activation, provides a tool for specific activation of endogenous genes, and introduces a new role for noncoding RNAs in the regulation of gene expression. These small RNAs are typically 21-nucleotide duplexes, and have been shown to activate a wide variety of genes in many cell types and across species. The application of this technology will prove invaluable for basic research through gain-of-function studies and potentially targeted gene activation for disease intervention. This chapter will cover what is currently defined on the mechanism of RNA activation, and will explore the possible application of this technology for novel therapeutics.
Copyright 2015, The Author(s).