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| Status |
Public on Aug 11, 2015 |
| Title |
TDP-43 can directly affect splicing profiles and isoform production of genes involved in the apoptotic and mitotic cellular pathways |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In recent times, high throughput screening analyses have broadly defined the RNA cellular targets of TDP-43, a nuclear factor involved in neurodegeneration. A common outcome of all these studies is that changing the expression levels of this protein can alter the expression of several hundred RNAs within cells. What still remains to be clarified is which changes represent direct cellular targets of TDP-43 or just secondary variations due to the general role played by this protein in RNA metabolism. Using a HTS-based splicing junction analysis we have now identified 162 splicing events that are consistent with being directly controlled by TDP-43. Validation of the data, both in neuronal and non-neuronal cell lines demonstrated that TDP-43 substantially alters the levels of isoform expression in four genes potentially important for neuropathology: MADD/IG20, STAG2, FNIP1, and BRD8. Most importantly, for MADD/IG20 and STAG2 these changes could also be confirmed at the protein level. These alterations were also observed in a cellular model that successfully mimics TDP-43 loss of function effects following its aggregation. These novel splicing events may represent potential biomarkers to predict disease onset, progression, and to test the efficacy of novel therapeutic agents to recover TDP-43 functional properties.
We have performed an HTS-based splicing junction analysis of a series of stable cell lines that lack TDP-43, overexpress this factor, or express an RNA-binding mutant, in order to find splicing events, potentially associated with neurodegenerativce diseases, regulated by this splicing factor.
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| Overall design |
Samples were analyzed in triplicate from:
The following samples were analyzed in triplicate: wild-type HEK-293 cells, siTDP43-treated HEK-293 cells, siTDP43-treated HEK-293 cells overexpressing a flagged-wildtype TDP-43, siTDP43-treated HEK-293 cells overexpressing a RNA-binding deficient mutant.
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| Contributor(s) |
Buratti E |
| Citation(s) |
26261209 |
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| Submission date |
Mar 24, 2015 |
| Last update date |
Nov 04, 2015 |
| Contact name |
Pierre de la Grange |
| E-mail(s) |
pierre.delagrange@genosplice.com
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| Organization name |
GenoSplice technology
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| Department |
Paris Biotech Santé
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| Street address |
29, rue du Faubourg Saint-Jacques
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| City |
Paris |
| ZIP/Postal code |
75014 |
| Country |
France |
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| Platforms (2) |
| GPL15106 |
[hjay] Affymetrix GeneChip Human HJAY Array |
| GPL17272 |
[hjay] Affymetrix GeneChip Human HJAY Array (gene array) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA279258 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67195_RAW.tar |
661.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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