Aurintricarboxylic acid decreases rna toxicity in a c. Elegans model of repeat expansions

Maya Braun, Shachar Shoshani, Anna Mellul-Shtern, Yuval Tabach

Research output: Contribution to journalArticlepeer-review

Abstract

Pathologic expansions of DNA nucleotide tandem repeats may generate toxic RNA that triggers disease phenotypes. RNA toxicity is the hallmark of multiple expansion repeat disorders, including myotonic dystrophy type 1 (DM1). To date, there are no available disease-modifying therapies for DM1. Our aim was to use drug repositioning to ameliorate the phenotype of affected individuals in a nematode model of DM1. As the RNA interference pathway plays a key role in mediating RNA toxicity, we investigated the effect of aurintricarboxylic acid. We demonstrated that by perturbing the RNA interference machinery using aurintricarboxylic acid, we could annihilate the RNA toxicity and ameliorate the phenotype. As our approach targets a universal disease mechanism, it is potentially relevant for more expansion repeat disorders.

Original languageEnglish
Article number910
JournalToxins
Volume13
Issue number12
DOIs
StatePublished - 20 Dec 2021

Keywords

  • C. elegans
  • CUG repeats
  • Drug repositioning
  • RNA interference
  • Small RNA pathway

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

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