RNA-Dependent Epigenetic Silencing Directs Transcriptional Downregulation Caused by Intronic 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

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)


Transcriptional downregulation caused by intronic triplet repeat expansions underlies diseases such as Friedreich's ataxia. This downregulation of gene expression is coupled with epigenetic changes, but the underlying mechanisms are unknown. Here, we show that an intronic GAA/TTC triplet expansion within the IIL1 gene of Arabidopsis thaliana results in accumulation of 24-nt short interfering RNAs (siRNAs) and repressive histone marks at the IIL1 locus, which in turn causes its transcriptional downregulation and an associated phenotype. Knocking down DICER LIKE-3 (DCL3), which produces 24-nt siRNAs, suppressed transcriptional downregulation of IIL1 and the triplet expansion-associated phenotype. Furthermore, knocking down additional components of the RNA-dependent DNA methylation (RdDM) pathway also suppressed both transcriptional downregulation of IIL1 and the repeat expansion-associated phenotype. Thus, our results show that triplet repeat expansions can lead to local siRNA biogenesis, which in turn downregulates transcription through an RdDM-dependent epigenetic modification. Triplet expansions within an Arabidopsis gene leads to local siRNA biogenesis and consequent transcriptional downregulation, suggesting how intronic repeat expansions may affect gene expression in other systems.

Original languageEnglish
Pages (from-to)1095-1105.e11
Number of pages23
Issue number5
Publication statusPublished - 23 Aug 2018


  • Arabidopsis
  • epigenetic silencing
  • Friedreich's ataxia
  • RdDM pathway
  • siRNAs
  • transcriptional downregulation
  • triplet repeat expansion

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