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GSE27218

GSE GEO
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Disrupted processing of long pre-mRNAs and widespread RNA missplicing are components of neuronal vulnerability from loss of nuclear TDP-43 (RNA-seq)

Organism: Mus musculus
Platform: GPL9250
Samples: 21
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Feb 10 2011
Last Updated: May 15 2019
Status: Public on Mar 03 2011
Contact: Gene,,Yeo (UCSD)

Relations

SubSeries of: GSE27394 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP005860 BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA141971

Summary

Cross-linking and immunoprecipitation coupled with high-throughput sequencing was used to identify binding sites within 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein which when mutated causes Amyotrophic Lateral Sclerosis (ALS). Use of massively parallel sequencing and splicing-sensitive junction arrays revealed that levels of 601 mRNAs are changed (including Fus/Tls, progranulin, and other transcripts encoding neurodegenerative disease-associated proteins) and 965 altered splicing events are detected (including in sortilin, the receptor for progranulin), following depletion of TDP-43 from adult brain with antisense oligonucleotides. RNAs whose levels are most depleted by reduction in TDP-43 are derived from genes with very long introns and which encode proteins involved in synaptic activity. Lastly, TDP-43 was found to auto-regulate its synthesis, in part by directly binding and enhancing splicing of an intron within the 3’ untranslated region of its own transcript, thereby triggering nonsense mediated RNA degradation.

Overall Design

RNAseq in control and Tdp-43 knockdown mouse striatum

Analysis (1 step)

View Data Processing
Processing steps for GSE27218
  1. Sequenced reads were trimmed for adaptor sequence, and masked for low-complexity or low-quality sequence, then mapped to mm8 whole genome using bowtie v0.12.2 with parameters -q -p 4 -e 100 -y -a -m 10 --best --strata

Supplementary Files (1)

GSE27218_RAW.tar Download
GEO Samples (21)

Dataset Citations (1)

Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43.
PMID 21358643 · 2011 · Nature neuroscience
Magdalini Polymenidou, Clotilde Lagier-Tourenne, Kasey R Hutt, Stephanie C Huelga, Jacqueline Moran, Tiffany Y Liang, Shuo-Chien Ling, Eveline Sun, Edward Wancewicz, Curt Mazur, Holly Kordasiewicz, Yalda Sedaghat, John Paul Donohue, Lily Shiue, C Frank Bennett, Gene W Yeo, Don W Cleveland

SRA Experiments (21) and Runs (21)

Total: 17166 MB
SRX043744 SRP005860 RNA-Seq SINGLE
GSM672528: brain_RNAseq_control-oligo_rep1.1
Sample: SRS173038
BioProject: PRJNA141971
BioSample: SAMN00216107
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107061 18475128 1330209216 758.28 SRR107061, SRR107061.sralite SRA
SRX043745 SRP005860 RNA-Seq SINGLE
GSM672529: brain_RNAseq_control-oligo_rep2.1
Sample: SRS173039
BioProject: PRJNA141971
BioSample: SAMN00216108
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107062 20263592 1458978624 845.6 SRR107062, SRR107062.sralite SRA
SRX043746 SRP005860 RNA-Seq SINGLE
GSM672530: brain_RNAseq_control-oligo_rep3.1
Sample: SRS173040
BioProject: PRJNA141971
BioSample: SAMN00216109
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107063 17439358 1255633776 701.34 SRR107063, SRR107063.sralite SRA
SRX043747 SRP005860 RNA-Seq SINGLE
GSM672531: brain_RNAseq_control-oligo_rep4.1
Sample: SRS173041
BioProject: PRJNA141971
BioSample: SAMN00216110
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107064 19332451 1391936472 786.18 SRR107064, SRR107064.sralite SRA
SRX043748 SRP005860 RNA-Seq SINGLE
GSM672532: brain_RNAseq_control-oligo_rep4.2
Sample: SRS173042
BioProject: PRJNA141971
BioSample: SAMN00216111
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107065 19042665 1371071880 772.1 SRR107065, SRR107065.sralite SRA
SRX043749 SRP005860 RNA-Seq SINGLE
GSM672533: brain_RNAseq_control-oligo_rep1.2
Sample: SRS173043
BioProject: PRJNA141971
BioSample: SAMN00216112
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107066 24426406 1758701232 905.94 SRR107066, SRR107066.sralite SRA
SRX043750 SRP005860 RNA-Seq SINGLE
GSM672534: brain_RNAseq_control-oligo_rep2.2
Sample: SRS173044
BioProject: PRJNA141971
BioSample: SAMN00216113
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107067 26814519 1930645368 1009.69 SRR107067, SRR107067.sralite SRA
SRX043751 SRP005860 RNA-Seq SINGLE
GSM672535: brain_RNAseq_control-oligo_rep2.3
Sample: SRS173045
BioProject: PRJNA141971
BioSample: SAMN00216114
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107068 27065143 1948690296 1011.91 SRR107068, SRR107068.sralite SRA
SRX043752 SRP005860 RNA-Seq SINGLE
GSM672536: brain_RNAseq_control-oligo_rep3.2
Sample: SRS173046
BioProject: PRJNA141971
BioSample: SAMN00216115
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107069 23094614 1662812208 819.86 SRR107069, SRR107069.sralite SRA
SRX043753 SRP005860 RNA-Seq SINGLE
GSM672537: brain_RNAseq_control-oligo_rep3.3
Sample: SRS173047
BioProject: PRJNA141971
BioSample: SAMN00216116
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107070 22687715 1633515480 818.03 SRR107070, SRR107070.sralite SRA
SRX043754 SRP005860 RNA-Seq SINGLE
GSM672538: brain_RNAseq_control-oligo_rep4.3
Sample: SRS173048
BioProject: PRJNA141971
BioSample: SAMN00216117
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: control anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107071 26505415 1908389880 993.33 SRR107071, SRR107071.sralite SRA
SRX043755 SRP005860 RNA-Seq SINGLE
GSM672539: brain_RNAseq_Tdp43-oligo_rep1.1
Sample: SRS173049
BioProject: PRJNA141971
BioSample: SAMN00216118
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107072 15548708 1119506976 780.28 SRR107072, SRR107072.sralite SRA
SRX043756 SRP005860 RNA-Seq SINGLE
GSM672540: brain_RNAseq_Tdp43-oligo_rep1.2
Sample: SRS173050
BioProject: PRJNA141971
BioSample: SAMN00216119
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107073 14777990 1064015280 731.02 SRR107073, SRR107073.sralite SRA
SRX043757 SRP005860 RNA-Seq SINGLE
GSM672541: brain_RNAseq_Tdp43-oligo_rep2.1
Sample: SRS173051
BioProject: PRJNA141971
BioSample: SAMN00216120
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107074 19756522 1422469584 676.6 SRR107074, SRR107074.sralite SRA
SRX043758 SRP005860 RNA-Seq SINGLE
GSM672542: brain_RNAseq_Tdp43-oligo_rep2.2
Sample: SRS173052
BioProject: PRJNA141971
BioSample: SAMN00216121
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107075 17781481 1280266632 600.42 SRR107075, SRR107075.sralite SRA
SRX043759 SRP005860 RNA-Seq SINGLE
GSM672543: brain_RNAseq_Tdp43-oligo_rep1.3
Sample: SRS173053
BioProject: PRJNA141971
BioSample: SAMN00216122
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107076 22306244 1606049568 673.43 SRR107076, SRR107076.sralite SRA
SRX043760 SRP005860 RNA-Seq SINGLE
GSM672544: brain_RNAseq_Tdp43-oligo_rep2.3
Sample: SRS173054
BioProject: PRJNA141971
BioSample: SAMN00216123
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107077 21930973 1579030056 667.45 SRR107077, SRR107077.sralite SRA
SRX043761 SRP005860 RNA-Seq SINGLE
GSM672545: brain_RNAseq_Tdp43-oligo_rep3.1
Sample: SRS173055
BioProject: PRJNA141971
BioSample: SAMN00216124
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107078 18836553 1356231816 796.6 SRR107078, SRR107078.sralite SRA
SRX043762 SRP005860 RNA-Seq SINGLE
GSM672546: brain_RNAseq_Tdp43-oligo_rep4.1
Sample: SRS173056
BioProject: PRJNA141971
BioSample: SAMN00216125
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107079 19714030 1419410160 811.97 SRR107079, SRR107079.sralite SRA
SRX043763 SRP005860 RNA-Seq SINGLE
GSM672547: brain_RNAseq_Tdp43-oligo_rep3.2
Sample: SRS173057
BioProject: PRJNA141971
BioSample: SAMN00216126
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107080 26676256 1920690432 998.67 SRR107080, SRR107080.sralite SRA
SRX043764 SRP005860 RNA-Seq SINGLE
GSM672548: brain_RNAseq_Tdp43-oligo_rep4.2
Sample: SRS173058
BioProject: PRJNA141971
BioSample: SAMN00216127
Platform: ILLUMINA
Instrument: Illumina Genome Analyzer II
Organism: Mus musculus
Sample attributes
source_name: Striatum
strain: C57BL/6
age: 8-10 weeks
treatment: Tdp-43 anti-sense oligo
Original files (1)
Striatum
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR107081 26567498 1912859856 1007.12 SRR107081, SRR107081.sralite SRA

Linked Publications (1)

Data Files (21)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
SRR107061 RNA-Seq 758.3 MB link
SRR107062 RNA-Seq 845.6 MB link
SRR107063 RNA-Seq 701.3 MB link
SRR107064 RNA-Seq 786.2 MB link
SRR107065 RNA-Seq 772.1 MB link
SRR107066 RNA-Seq 905.9 MB link
SRR107067 RNA-Seq 1009.7 MB link
SRR107068 RNA-Seq 1011.9 MB link
SRR107069 RNA-Seq 819.9 MB link
SRR107070 RNA-Seq 818.0 MB link
SRR107071 RNA-Seq 993.3 MB link
SRR107072 RNA-Seq 780.3 MB link
SRR107073 RNA-Seq 731.0 MB link
SRR107074 RNA-Seq 676.6 MB link
SRR107075 RNA-Seq 600.4 MB link
SRR107076 RNA-Seq 673.4 MB link
SRR107077 RNA-Seq 667.4 MB link
SRR107078 RNA-Seq 796.6 MB link
SRR107079 RNA-Seq 812.0 MB link
SRR107080 RNA-Seq 998.7 MB link
SRR107081 RNA-Seq 1007.1 MB link