Identification of genes in toxicity pathways of trinucleotide-repeat RNA in C. elegans

Susana M.D.A. Garcia, Yuval Tabach, Guinevere F. Lourenço, Maria Armakola, Gary Ruvkun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Myotonic dystrophy disorders are caused by expanded CUG repeats in noncoding regions. Here we used Caenorhabditis elegans expressing CUG repeats to identify genes that modulate the toxicity of such repeats. We identified 15 conserved genes that function as suppressors or enhancers of CUG repeat-induced toxicity and that modulate formation of nuclear foci by CUG-repeat RNA. These genes regulate CUG repeat-induced toxicity through distinct mechanisms including RNA export and clearance, thus suggesting that CUG-repeat toxicity is mediated by multiple pathways. A subset of the genes are also involved in other degenerative disorders. The nonsense-mediated mRNA decay (NMD) pathway has a conserved role in regulating CUG-repeat-RNA transcript levels and toxicity, and NMD recognition of toxic RNAs depends on 3' €2-untranslated-region GC-nucleotide content. Our studies suggest a broader surveillance role for NMD in which variations in this pathway influence multiple degenerative diseases.

Original languageEnglish (US)
Pages (from-to)712-720
Number of pages9
JournalNature Structural and Molecular Biology
Issue number8
StatePublished - Aug 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology


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