Genetic Variations Creating MicroRNA Target Sites in the FXN 3′-UTR Affect Frataxin Expression in Friedreich Ataxia.

Genetic Variations Creating MicroRNA Target Sites in the FXN 3′-UTR Affect Frataxin Expression in Friedreich Ataxia. Simonetta Bandiera ,François Cartault, Anne-Sophie Jannot, Elie Hatem, Muriel Girard, Laila Rifai, Clemence Loiseau, Arnold Munnich, Stanislas Lyonnet, Alexandra Henrion-Caude. (2013)PLoS ONE 8(1): e54791. doi:10.1371/journal.pone.0054791

We found that this FRDA 3′-UTR conferred a 1.2-fold decrease in the expression of a reporter gene versus the alternative haplotype configuration. We established that differential targeting by miRNA could account for this functional variability. We specifically demonstrated the involvement of miR-124 (i.e hsa-mir-124-3p) in the down-regulation of FRDA-3′-UTR. Our results suggest for the first time that post-transcriptional regulation of frataxin occurs through the 3′-UTR and involves miRNA targeting. We propose that the involvement of miRNAs in a FRDA-specific regulation of frataxin may provide a rationale to increase residual levels of frataxin through miRNA-inhibitory molecules.

OPEN ACCESS