Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs

Clare L van Eyk, Louise V O'Keefe, Kynan T Lawlor, Saumya E Samaraweera, Catherine J McLeod, Gareth R Price, Deon J Venter, Robert I Richards

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Recent evidence supports a role for RNA as a common pathogenic agent in both the 'polyglutamine' and 'untranslated' dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin-forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcript levels as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease-associated repeat sequences--CAG, CUG and AUUCU--were specifically expressed in the neurons of Drosophila and resultant common transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3-β signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.

Original languageEnglish
Pages (from-to)2783-94
Number of pages12
JournalHuman Molecular Genetics
Volume20
Issue number14
DOIs
Publication statusPublished - 15 Jul 2011
Externally publishedYes

Keywords

  • Animals
  • Drosophila Proteins
  • Drosophila melanogaster
  • Gene Expression
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • Neurodegenerative Diseases
  • Proto-Oncogene Proteins c-akt
  • RNA
  • Repetitive Sequences, Nucleic Acid
  • Signal Transduction
  • Journal Article
  • Research Support, Non-U.S. Gov't

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