FAST-1 antisense RNA epigenetically alters FXN expression

Hajar Mikaeili, Madhavi Sandi, Aurélien Bayot, Sahar Al-Mahdawi & Mark A. Pook; Scientific Reports, volume 8, Article number: 17217 (2018). doi:10.1038/s41598-018-35639-2

Our results show that knocking down FAST-1 in FRDA fibroblast cells increases FXN gene expression (Fig. 10). Therefore, it can be concluded that, since FAST-1 is associated with epigenetic repression of the FXN gene, inhibition of FAST-1 may be an approach to increase the FXN transcripts and stimulate subsequent protein expression. Indeed, our results demonstrate that knocking down FAST-1 in FRDA results in a significant increase in aconitase enzyme activity, a good indicator of frataxin function within cells. Our data suggest that since FAST-1 is associated with FXN gene silencing, inhibition of FAST-1 may be an approach for FRDA therapy. Considering the nature of NATs and the fact that many currently available drugs would not affect the activity of non-coding RNA molecules, developing new methods to disrupt the function of NATs seems necessary.