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| Status |
Public on Jul 27, 2020 |
| Title |
Loss of Tdp-43 disrupts the axonal transcriptome of motoneurons accompanied by impaired axonal translation and mitochondria function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Protein inclusions containing the RNA-binding protein TDP-43 are a pathological hallmark of amyotrophic lateral sclerosis and other neurodegenerative disorders. The loss of TDP-43 function that is associated with these inclusions affects post-transcriptional processing of RNAs in multiple ways including pre-mRNA splicing, nucleocytoplasmic transport, modulation of mRNA stability and translation. In contrast, less is known about the role of TDP-43 in axonal RNA metabolism in motoneurons. Here we show that depletion of Tdp-43 in primary motoneurons affects axon growth. This defect is accompanied by subcellular transcriptome alterations in the axonal and somatodendritic compartment. The axonal localization of transcripts encoding components of the cytoskeleton, the translational machinery and transcripts involved in mitochondrial energy metabolism were particularly affected by loss of Tdp-43. Accordingly, we observed reduced protein synthesis and disturbed mitochondrial functions in axons of Tdp-43-depleted motoneurons. Treatment with nicotinamide rescued the axon growth defect associated with loss of Tdp-43. These results show that Tdp-43 depletion in motoneurons affects several pathways integral to axon health indicating that loss of TDP-43 function could thus make a major contribution to axonal pathomechanisms in ALS.
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| Overall design |
Total number of samples is 20. Gene expression data from axonal compartment of cultured control motoneurons, somatodendritic compartment of cultured control motoneurons, axonal compartment of cultured Tdp-43 knockdown motoneurons, and somatodendritic compartment of cultured Tdp-43 knockdown motoneurons.
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| Contributor(s) |
Briese M, Saal-Bauernschubert L, Lüningschrör P, Moradi M, Dombert B, Surrey V, Appenzeller S, Deng C, Jablonka S, Sendtner M |
| Citation(s) |
32709255 |
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| Submission date |
Mar 26, 2020 |
| Last update date |
Apr 12, 2023 |
| Contact name |
Silke Appenzeller |
| E-mail(s) |
[email protected]
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| Organization name |
University Wuerzburg
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| Street address |
Schweinfurter Str. 28
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| City |
Würzburg |
| ZIP/Postal code |
97076 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA615680 |
| SRA |
SRP254218 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE147607_RAW.tar |
19.8 Mb |
(http)(custom) |
TAR (of CSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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