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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 30, 2019 |
| Title |
Tau drives translational selectivity by interacting with ribosomal proteins |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
There is a fundamental gap in understanding the consequences of tau-ribosome interactions. Tau oligomers and filaments hinder protein synthesis in vitro, and they associate strongly with ribosomes in vivo. Here, we investigated the consequences of tau interactions with ribosomes in vivo and in human brain tissues to identify tau as a direct modulator of ribosomal selectivity. We performed microarrays and nascent proteomics to measure changes in protein synthesis using rTg4510 tau transgenic mice. We determined that tau expression differentially shifts the transcriptome and the proteome and that the synthesis of ribosomal proteins is reversibly dependent on tau levels. We further extended these results to human brains and show that tau pathologically interacts with ribosomal protein S6 (rpS6 or S6). Consequently, synthesis of ribosomal proteins coded by 5’TOP-mRNAs was reduced under tauopathic conditions in Alzheimer’s disease brains. Our data establish tau as a driver of RNA translation selectivity. Moreover, considering that regulation of protein synthesis is critical to learning and memory, aberrant tau-ribosome interactions in disease could explain the linkage between virtually every tauopathy and cognitive impairment and memory decline.
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| Overall design |
Nontransgenic mice and rTg4510 tau transgenic mice were fed either normal feed or doxycycline to suppress transgenic tau expression. Biological replicates: Non + veh = 3, Non + dox = 2, Tg + veh = 3, Tg + dox = 3
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| Contributor(s) |
Shon KA, Hamm MJ, Shelby ME, Blaine WE, Nation GK, Emad CA, Jing C, Juan Pablo A, Haining Z, Eric BM, Jose AF |
| Citation(s) |
30759285 |
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| Submission date |
Oct 15, 2018 |
| Last update date |
Apr 08, 2019 |
| Contact name |
Jose F Abisambra |
| E-mail(s) |
[email protected]
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| Organization name |
University of Florida
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| Department |
Department of Neuroscience & Center for Translational Research in Neurodegenerative Research
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| Lab |
Abisambra Lab
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| Street address |
1275 Center Dr
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| City |
Gainesville |
| State/province |
FL |
| ZIP/Postal code |
32610 |
| Country |
USA |
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| Platforms (1) |
| GPL20775 |
[MTA-1_0] Affymetrix Mouse Transcriptome Array 1.0 [transcript (gene) CSV version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA496504 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE121264_RAW.tar |
281.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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