GSE86040
GSE GEOHNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_eCLIP_human_iPSC_MN]
Organism:
Homo sapiens
Platform:
GPL16791
Samples:
14
Experiment Types:
Other
Submitted:
Aug 25 2016
Last Updated:
May 15 2019
Status:
Public on Oct 20 2016
Contact:
Gene,,Yeo (UCSD)
Relations
SubSeries of: GSE86464
BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA341995
SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP086700
Summary
HnRNPA2B1 encodes an RNA binding protein associated with neurodegenerative disorders. However, its function in the nervous system is unclear. Transcriptome-wide cross-linking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ~2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. Loss of hnRNP A2/B1 results in alternative splicing, including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. Inclusion of the DAO exon is also reduced in transgenic ALS mice models. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells demonstrate gain-of-mutant-dependent splicing differences. Mutant motor neurons also exhibit increased hnRNP A2/B1 localization to cytoplasmic granules during stress, which are abrogated by a small molecule CA43. Our findings and cellular resource identify RNA networks affected in loss of normal and mutated hnRNP A2/B1 with broad relevance to neurodegeneration.
Overall Design
eCLIP-seq in human iPSC-MNs
Analysis (6 steps)
View Data Processing
Processing steps for GSE86040
- Reads were demultiplexed using custom scripts and the randomer was appended to the read name.
- Reads were trimmed, filtered for repetitive elements, and mapped to human genome assembly hg19 as described in iCLIP computational analysis.
- PCR duplicated reads were removed based on the start positions of read1, read2, and the sequence of the randomer. eCLIP peaks were identified using CLIPPER with parameters âs hg19 âo âbonferroni âsuperlocal --threshold-method binomial --save-pickle (Lovci et al.
- NSMB, 2013).
- Peak strength was then normalized against a size matched input by calculating fold enrichment of number of reads in IP versus number of reads in size matched input.
- Peaks were called significant if the number of reads in IP was greater than the number of reads in input and the the peaks a Bonferroni corrected fisher exact p-value of less than .05.
Supplementary Files (1)
GSE86040_RAW.tar
Download
Dataset Citations (1)
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.
PMID 27773581
· 2016
· Neuron
Fernando J Martinez, Gabriel A Pratt, Eric L Van Nostrand, Ranjan Batra, Stephanie C Huelga, Katannya Kapeli, Peter Freese, Seung J Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C Wang, Julia K Nussbacher, Sara M Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, C Frank Bennett, Manuel Ares, Christopher B Burge, J Paul Taylor, Frank Rigo, Gene W Yeo
SRA Experiments (14) and Runs (21)
Total: 6145 MBGSM2292508: hnRNPA2/B1_eCLIP_001; Homo sapiens; RIP-Seq
Sample: SRS1672475
BioProject: PRJNA341995
BioSample: SAMN05730923
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292509: hnRNPA2/B1_eCLIP_002; Homo sapiens; RIP-Seq
Sample: SRS1672478
BioProject: PRJNA341995
BioSample: SAMN05730922
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175308 | 14925547 | 1567182435 | 606.43 | F1_IN_A2B1_ATTACTCG-TATAGCCT_L008_R1.unassigned.randomer.fastq.gz, F1… | SRA |
GSM2292510: hnRNPA2/B1_eCLIP_003; Homo sapiens; RIP-Seq
Sample: SRS1672477
BioProject: PRJNA341995
BioSample: SAMN05730921
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292511: hnRNPA2/B1_eCLIP_004; Homo sapiens; RIP-Seq
Sample: SRS1672476
BioProject: PRJNA341995
BioSample: SAMN05730920
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175311 | 12414937 | 1303568385 | 506.55 | F2_IN_A2B1_CGCTCATT-TATAGCCT_L008_R1.unassigned.randomer.fastq.gz, F2… | SRA |
GSM2292512: hnRNPA2/B1_eCLIP_005; Homo sapiens; RIP-Seq
Sample: SRS1672479
BioProject: PRJNA341995
BioSample: SAMN05730919
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292513: hnRNPA2/B1_eCLIP_006; Homo sapiens; RIP-Seq
Sample: SRS1672480
BioProject: PRJNA341995
BioSample: SAMN05730933
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175314 | 18111907 | 1901750235 | 733.51 | F3_IN_A2B1_ATTCAGAA-TATAGCCT_L008_R1.unassigned.randomer.fastq.gz, F3… | SRA |
GSM2292514: hnRNPA2/B1_eCLIP_007; Homo sapiens; RIP-Seq
Sample: SRS1672481
BioProject: PRJNA341995
BioSample: SAMN05730932
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292515: hnRNPA2/B1_eCLIP_008; Homo sapiens; RIP-Seq
Sample: SRS1672482
BioProject: PRJNA341995
BioSample: SAMN05730931
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175317 | 17956341 | 1885415805 | 735.25 | F4_IN_A2B1_ATTACTCG-ATAGAGGC_L008_R1.unassigned.randomer.fastq.gz, F4… | SRA |
GSM2292516: hnRNPA2/B1_eCLIP_009; Homo sapiens; RIP-Seq
Sample: SRS1672483
BioProject: PRJNA341995
BioSample: SAMN05730930
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292517: hnRNPA2/B1_eCLIP_010; Homo sapiens; RIP-Seq
Sample: SRS1672484
BioProject: PRJNA341995
BioSample: SAMN05730929
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175320 | 10861702 | 1140478710 | 447.83 | F5_IN_A2B1_CGCTCATT-ATAGAGGC_L008_R1.unassigned.randomer.fastq.gz, F5… | SRA |
GSM2292518: hnRNPA2/B1_eCLIP_011; Homo sapiens; RIP-Seq
Sample: SRS1672485
BioProject: PRJNA341995
BioSample: SAMN05730928
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292519: hnRNPA2/B1_eCLIP_012; Homo sapiens; RIP-Seq
Sample: SRS1672486
BioProject: PRJNA341995
BioSample: SAMN05730927
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175323 | 8330843 | 874738515 | 340.95 | F6_IN_A2B1_ATTCAGAA-ATAGAGGC_L008_R1.unassigned.randomer.fastq.gz, F6… | SRA |
GSM2292520: hnRNPA2/B1_eCLIP_013; Homo sapiens; RIP-Seq
Sample: SRS1672487
BioProject: PRJNA341995
BioSample: SAMN05730926
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: hnRNP A2/B1
vendor: Genetex
catalog number: GTX127928
lot number: 41094
Original files (1)
iPSC derived motor neurons
GSM2292521: hnRNPA2/B1_eCLIP_014; Homo sapiens; RIP-Seq
Sample: SRS1672488
BioProject: PRJNA341995
BioSample: SAMN05730925
Platform: ILLUMINA
Instrument: Illumina HiSeq 2500
Organism: Homo sapiens
Sample attributes
source_name: iPSC derived motor neurons
cell line: CTRL.JCV
age: 28 days
tissue type: iPSC-MNs
antibody: null
vendor: null
catalog number: null
lot number: null
Original files (1)
iPSC derived motor neurons
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR4175326 | 10787392 | 1132676160 | 446.35 | F7_IN_IgG_ATTACTCG-CCTATCCT_L008_R1.unassigned.randomer.fastq.gz, F7_… | SRA |
Linked Publications (1)
Data Files (21)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | F1_IN_A2B1_ATTACTCG-TATAGCCT_L008_R1.unassigned.random… | RIP-Seq | 606.4 MB | link | |||
| — | F1_IP_A2B1_TCCGGAGA-TATAGCCT_L008_R1.A01_F1_IP_mnCLIP_… | RIP-Seq | 225.5 MB | link | |||
| — | F1_IP_A2B1_TCCGGAGA-TATAGCCT_L008_R1.B06_F1_IP_mnCLIP_… | RIP-Seq | 156.4 MB | link | |||
| — | F2_IN_A2B1_CGCTCATT-TATAGCCT_L008_R1.unassigned.random… | RIP-Seq | 506.5 MB | link | |||
| — | F2_IP_A2B1_GAGATTCC-TATAGCCT_L008_R1.C01_F2_IP_mnCLIP_… | RIP-Seq | 245.9 MB | link | |||
| — | F2_IP_A2B1_GAGATTCC-TATAGCCT_L008_R1.D08fixed_F2_IP_mn… | RIP-Seq | 138.8 MB | link | |||
| — | F3_IN_A2B1_ATTCAGAA-TATAGCCT_L008_R1.unassigned.random… | RIP-Seq | 733.5 MB | link | |||
| — | F3_IP_A2B1_GAATTCGT-TATAGCCT_L008_R1.A01_F3_IP_mnCLIP_… | RIP-Seq | 140.0 MB | link | |||
| — | F3_IP_A2B1_GAATTCGT-TATAGCCT_L008_R1.B06_F3_IP_mnCLIP_… | RIP-Seq | 88.0 MB | link | |||
| — | F4_IN_A2B1_ATTACTCG-ATAGAGGC_L008_R1.unassigned.random… | RIP-Seq | 735.2 MB | link | |||
| — | F4_IP_A2B1_TCCGGAGA-ATAGAGGC_L008_R1.C01_F4_IP_mnCLIP_… | RIP-Seq | 392.8 MB | link | |||
| — | F4_IP_A2B1_TCCGGAGA-ATAGAGGC_L008_R1.D08fixed_F4_IP_mn… | RIP-Seq | 122.7 MB | link | |||
| — | F5_IN_A2B1_CGCTCATT-ATAGAGGC_L008_R1.unassigned.random… | RIP-Seq | 447.8 MB | link | |||
| — | F5_IP_A2B1_GAGATTCC-ATAGAGGC_L008_R1.A01_F5_IP_mnCLIP_… | RIP-Seq | 282.0 MB | link | |||
| — | F5_IP_A2B1_GAGATTCC-ATAGAGGC_L008_R1.B06_F5_IP_mnCLIP_… | RIP-Seq | 108.2 MB | link | |||
| — | F6_IN_A2B1_ATTCAGAA-ATAGAGGC_L008_R1.unassigned.random… | RIP-Seq | 340.9 MB | link | |||
| — | F6_IP_A2B1_GAATTCGT-ATAGAGGC_L008_R1.C01_F6_IP_mnCLIP_… | RIP-Seq | 315.6 MB | link | |||
| — | F6_IP_A2B1_GAATTCGT-ATAGAGGC_L008_R1.D08fixed_F6_IP_mn… | RIP-Seq | 111.7 MB | link | |||
| — | F7_IN_IgG_ATTACTCG-CCTATCCT_L008_R1.unassigned.randome… | RIP-Seq | 446.3 MB | link | |||
| — | F7_IP_IgG_ATTCAGAA-CCTATCCT_L008_R1.A01_F7_IP_mnCLIP_I… | RIP-Seq | 102.4 KB | link | |||
| — | F7_IP_IgG_ATTCAGAA-CCTATCCT_L008_R1.B06_F7_IP_mnCLIP_I… | RIP-Seq | 112.6 KB | link |