MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression

Paugh SW, Coss DR, Bao J, Laudermilk LT, Grace CR, Ferreira AM, M. Brett Waddell, Granger Ridout, Deanna Naeve, Michael Leuze, Philip F. LoCascio, John C. Panetta, Mark R. Wilkinson, Ching-Hon Pui, Clayton W. Naeve, Edward C. Uberbacher, Erik J. Bonten, William E. Evans (2016); PLoS Comput Biol 12(2): e1004744. doi:10.1371/journal.pcbi.1004744

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Friedreichs ataxia, the most common form of ataxia in humans, is caused by the expansion of a (GAA)n repeat in intron 1 of the Frataxin gene, which in turn results in transcriptional silencing, presumably because of the triplex-forming potential of the (GAA)n repeat. This suggests that, not only may the formation of DNA triplexes be a well-conserved and essential mechanism to regulate gene transcription, but that stable or prolonged triplex formation may have undesirable consequences.

 MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression