|Comment on four Science papers
Taken together, it seems that the findings propose that active genes remain "poised" for transcription by making short RNAs in the regions of their promoter, as if keeping the engine running. This appears to be a general phenomenon, not specific to AD-related genes per se. On the other hand, these short RNAs have the potential themselves to be regulated (e.g., by miRNAs). Although there is no evidence to support such a speculation, any new means of regulating gene regulation opens a new crack in the door of manipulating gene regulation for the treatment of disease. It will be quite interesting to see how this story plays out.
Wherever new gene regulation is discovered, there is the potential that disease-associated mutations may exist that could have clinical consequences. These papers emphasize that relying solely on identification of coding region mutations in disease may be too narrow an approach—the entire structure of a gene, from upstream (promoter-proximal) regions, through alternative exons and 3' ends, will need to be...