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Status |
Public on Apr 28, 2011 |
Title |
Perturbation of the Akt/Gsk3-beta signaling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs |
Organism |
Drosophila melanogaster |
Experiment type |
Expression profiling by array
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Summary |
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 transcripts 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, early, 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.
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Overall design |
The heads from newly eclosed Male Drosophila were used for RNA extraction and profiling on Affymetrix Drosophile Genome 2.0 microarrays. Twenty samples were analysed, representing control and experimental lines. Two independently derived control lines were used in each exeriment, totaling 4 samples. The tri-nucleotide repeats (CAG, CUG, CAA) were represented by three independently derived two transgene insertion lines each in one experiment and two independent four transgene insertion lines each in a second experiment, totaling 15 samples. A single four transgene insertion line was analysed for AUUCU. Candidates were selected from the pool of transcripts which showed a ‘present’ call in either all independent lines for a particular repeat sequence, or in all samples for the elav- GAL4/+ control in that experiment. Where possible, T-tests were performed on raw values to determine samples that showed a significant difference with a P-value < 0.05.
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Contributor(s) |
van Eyk CL, O'Keefe LV, Lawlor KT, Samaraweera SE, McLeod CJ, Price GR, Venter DJ, Richards RI |
Citation(s) |
21518731 |
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Submission date |
Feb 09, 2011 |
Last update date |
Aug 28, 2018 |
Contact name |
Gareth Price |
E-mail(s) |
[email protected]
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Phone |
61413289611
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Organization name |
Queensland Facility for Advanced Bioinformatics
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Street address |
Carmody Road
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City |
Brisbane |
State/province |
Queensland |
ZIP/Postal code |
4072 |
Country |
Australia |
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Platforms (1) |
GPL1322 |
[Drosophila_2] Affymetrix Drosophila Genome 2.0 Array |
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Samples (20)
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GSM671699 |
Drosophila heads 0-3 days_elav c155>+_rep1 |
GSM671700 |
Drosophila heads 0-3 days_elav c155>+_rep2 |
GSM671701 |
Drosophila heads 0-3 days_elav c155>2x rCAG_independent line 2 |
GSM671702 |
Drosophila heads 0-3 days_elav c155>2x rCAG_independent line 1 |
GSM671703 |
Drosophila heads 0-3 days_elav c155>2x rCAG_independent line 3 |
GSM671704 |
Drosophila heads 0-3 days_elav c155>2x rCUG_independent line 1 |
GSM671705 |
Drosophila heads 0-3 days_elav c155>2x rCUG_independent line 2 |
GSM671706 |
Drosophila heads 0-3 days_elav c155>2x rCUG_independent line 3 |
GSM671707 |
Drosophila heads 0-3 days_elav c155>2x rCAA_independent line 1 |
GSM671708 |
Drosophila heads 0-3 days_elav c155>2x rCAA_independent line 3 |
GSM671709 |
Drosophila heads 0-3 days_elav c155>2x rCAA_independent line 2 |
GSM671710 |
Drosophila heads 0-3 days_elavII>+_rep1 |
GSM671711 |
Drosophila heads 0-3 days_elavII>+_rep2 |
GSM671712 |
Drosophila heads 0-3 days_elavII>4x rCAG_independent line 2 |
GSM671713 |
Drosophila heads 0-3 days_elavII>4x rCAG_independent line 1 |
GSM671714 |
Drosophila heads 0-3 days_elavII>4x rCUG_independent line 2 |
GSM671715 |
Drosophila heads 0-3 days_elavII>4x rCUG_independent line 1 |
GSM671716 |
Drosophila heads 0-3 days_elavII>4x rCAA_independent line 2 |
GSM671717 |
Drosophila heads 0-3 days_elavII>4x rCAA_independent line 1 |
GSM671718 |
Drosophila heads 0-3 days_elavII>4x rAUUCU_independent line 1 |
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Relations |
BioProject |
PRJNA137367 |
Supplementary file |
Size |
Download |
File type/resource |
GSE27178_RAW.tar |
41.5 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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