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| Status |
Public on Jul 05, 2016 |
| Title |
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [array] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3’ untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease.
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| Overall design |
RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns
This Series represents array sample(s).
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| Contributor(s) |
Kapeli K, Pratt G, Vu AQ, Hutt KR, Martinez FJ, Sundararaman B, Batra R, Freese P, Lambert NJ, Huelga SC, Chun S, Liang TY, Chang J, Hoon S, Donohue JP, Shiue L, Zhang J, Zhu H, Cambi F, Kasarskis E, Ares M Jr, Burge CB, Ravits J, Rigo F, Yeo GW |
| Citation(s) |
27378374 |
| Submission date |
Feb 08, 2016 |
| Last update date |
Oct 04, 2016 |
| Contact name |
Gene Yeo |
| E-mail(s) |
geneyeo@ucsd.edu
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| Organization name |
UCSD
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| Street address |
2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL13185 |
[mjay] Custom Affymetrix Mouse Exon Junction Array |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE77707 |
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses |
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| Relations |
| BioProject |
PRJNA311232 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77699_RAW.tar |
492.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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