Paul J Mintz, Vikash Reebye, Pål Sætrom, John J Rossi & Nagy A Habib
The next frontier in RNA biology is the advancement of RNA therapeutics and cellular reprogramming for unmet clinical needs. Since the discovery of post-transcriptional RNA interference (RNAi) by Fire and Mello, the RNA field has made tremendous progress, and small double-stranded RNAs (dsRNAs) play a pivotal role in our understanding of gene regulation. These small RNA molecules are known as non-coding RNAs (ncRNA) because they do not translate into biological proteins. The best classical examples and highly studied ncRNAs are microRNAs (miRNA) and small interfering RNAs (siRNA). They are essential in gene regulation through their ability to suppress target genes. Over the years, many other types of ncRNA have been identified such as long non-coding RNAs (lnc-RNA), Piwi-interacting RNA (piRNA), enhancer RNAs (eRNA), and extracellular RNAs (exRNA). This editorial will not cover these ncRNAs but only mention them in passing since they are already the subject of excellent published review articles. Rather, we will focus on another class of lesser known ncRNA called small/short activation RNAs (saRNA), or antigene RNAs (agRNA), due to their unique properties and controversial status. As the name suggests, these are short stretches of dsRNA molecules similar to siRNAs but with a unique ability to turn on genes rather than suppress them.