RNA-Dependent Epigenetic Silencing Directs Transcriptional Downregulation Caused by In- tronic Repeat Expansions

Hannes Eimer, Sridevi Sureshkumar, Avilash Singh Yadav, Calvin Kraupner-Taylor, Champa Bandaranayake, Andrei Seleznev, Tamblyn Thomason, Stephen J. Fletcher, Stephanie Frances Gordon, Bernard J. Carroll, Sureshkumar Balasubramanian; Cell Cell 174, 1–11 August 23, 2018, doi:10.1016/j.cell.2018.06.044

we have demonstrated that triplet expansions in transcribed regions of the genome have the potential to generate siRNAs, which in turn can target the locus harboring the repeat expansion for epigenetic gene silencing. Epigenetic changes have been implicated in several triplet expansion disorders. It has also been suggested that the repeats that undergo expansion have a distinct association with epigenetic features. Our findings reinforce the importance of epigenetic changes in establishing the disease state caused by triplet repeat expansions. It would be interesting to assess whether siRNA-mediated epigenetic silencing is of significance in triplet expansion diseases such as FRDA in the human system. Future studies should explore additional components of this pathway involving chromatin modifications that result from trinucleotide repeat expansions.

 RNA-Dependent Epigenetic Silencing Directs Transcriptional Downregulation Caused by In- tronic Repeat Expansions