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GSE86040

GSE GEO
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HNRNPA2B1 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
  1. Reads were demultiplexed using custom scripts and the randomer was appended to the read name.
  2. Reads were trimmed, filtered for repetitive elements, and mapped to human genome assembly hg19 as described in iCLIP computational analysis.
  3. 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 –s hg19 –o –bonferroni –superlocal --threshold-method binomial --save-pickle (Lovci et al.
  4. NSMB, 2013).
  5. 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.
  6. 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
GEO Samples (14)
GSM2292508 GSM2292509 GSM2292510 GSM2292511 GSM2292512 GSM2292513 GSM2292514 GSM2292515 GSM2292516 GSM2292517 GSM2292518 GSM2292519 GSM2292520 GSM2292521

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 MB
SRX2140552 SRP086700 RIP-Seq PAIRED
GSM2292508: 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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175306 6170630 604721740 225.54 F1_IP_A2B1_TCCGGAGA-TATAGCCT_L008_R1.A01_F1_IP_mnCLIP_A2B1_high_1_hnR… SRA
SRR4175307 4228769 414419362 156.4 F1_IP_A2B1_TCCGGAGA-TATAGCCT_L008_R1.B06_F1_IP_mnCLIP_A2B1_high_1_hnR… SRA
SRX2140553 SRP086700 RIP-Seq PAIRED
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
SRX2140554 SRP086700 RIP-Seq PAIRED
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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175309 6809024 667284352 245.89 F2_IP_A2B1_GAGATTCC-TATAGCCT_L008_R1.C01_F2_IP_mnCLIP_A2B1_high_2_hnR… SRA
SRR4175310 3774086 369860428 138.85 F2_IP_A2B1_GAGATTCC-TATAGCCT_L008_R1.D08fixed_F2_IP_mnCLIP_A2B1_high_… SRA
SRX2140555 SRP086700 RIP-Seq PAIRED
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
SRX2140556 SRP086700 RIP-Seq PAIRED
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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175312 3862740 378548520 140.0 F3_IP_A2B1_GAATTCGT-TATAGCCT_L008_R1.A01_F3_IP_mnCLIP_A2B1_med_1_hnRN… SRA
SRR4175313 2390046 234224508 87.99 F3_IP_A2B1_GAATTCGT-TATAGCCT_L008_R1.B06_F3_IP_mnCLIP_A2B1_med_1_hnRN… SRA
SRX2140557 SRP086700 RIP-Seq PAIRED
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
SRX2140558 SRP086700 RIP-Seq PAIRED
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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175315 10430113 1022151074 392.8 F4_IP_A2B1_TCCGGAGA-ATAGAGGC_L008_R1.C01_F4_IP_mnCLIP_A2B1_med_2_hnRN… SRA
SRR4175316 3213283 314901734 122.72 F4_IP_A2B1_TCCGGAGA-ATAGAGGC_L008_R1.D08fixed_F4_IP_mnCLIP_A2B1_med_2… SRA
SRX2140559 SRP086700 RIP-Seq PAIRED
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
SRX2140560 SRP086700 RIP-Seq PAIRED
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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175318 7713357 755908986 281.99 F5_IP_A2B1_GAGATTCC-ATAGAGGC_L008_R1.A01_F5_IP_mnCLIP_A2B1_low_1_hnRN… SRA
SRR4175319 2916462 285813276 108.23 F5_IP_A2B1_GAGATTCC-ATAGAGGC_L008_R1.B06_F5_IP_mnCLIP_A2B1_low_1_hnRN… SRA
SRX2140561 SRP086700 RIP-Seq PAIRED
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
SRX2140562 SRP086700 RIP-Seq PAIRED
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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175321 8596302 842437596 315.61 F6_IP_A2B1_GAATTCGT-ATAGAGGC_L008_R1.C01_F6_IP_mnCLIP_A2B1_low_2_hnRN… SRA
SRR4175322 3001963 294192374 111.67 F6_IP_A2B1_GAATTCGT-ATAGAGGC_L008_R1.D08fixed_F6_IP_mnCLIP_A2B1_low_2… SRA
SRX2140563 SRP086700 RIP-Seq PAIRED
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
SRX2140564 SRP086700 RIP-Seq PAIRED
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
Runs (2)
Run Spots Bases Size (MB) Files Link
SRR4175324 331 32438 0.1 F7_IP_IgG_ATTCAGAA-CCTATCCT_L008_R1.A01_F7_IP_mnCLIP_IgG_high_1_hnRNP… SRA
SRR4175325 509 49882 0.11 F7_IP_IgG_ATTCAGAA-CCTATCCT_L008_R1.B06_F7_IP_mnCLIP_IgG_high_1_hnRNP… SRA
SRX2140565 SRP086700 RIP-Seq PAIRED
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)

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.
Neuron · 2016

Data Files (42)

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
— SRR4175306_GSM2292508 RIP-Seq 225.0 MB link
— SRR4175307_GSM2292508 RIP-Seq 156.0 MB link
— SRR4175308_GSM2292509 RIP-Seq 606.0 MB link
— SRR4175309_GSM2292510 RIP-Seq 245.0 MB link
— SRR4175310_GSM2292510 RIP-Seq 138.0 MB link
— SRR4175311_GSM2292511 RIP-Seq 506.0 MB link
— SRR4175312_GSM2292512 RIP-Seq 140.0 MB link
— SRR4175313_GSM2292512 RIP-Seq 87.0 MB link
— SRR4175314_GSM2292513 RIP-Seq 733.0 MB link
— SRR4175315_GSM2292514 RIP-Seq 392.0 MB link
— SRR4175316_GSM2292514 RIP-Seq 122.0 MB link
— SRR4175317_GSM2292515 RIP-Seq 735.0 MB link
— SRR4175318_GSM2292516 RIP-Seq 281.0 MB link
— SRR4175319_GSM2292516 RIP-Seq 108.0 MB link
— SRR4175320_GSM2292517 RIP-Seq 447.0 MB link
— SRR4175321_GSM2292518 RIP-Seq 315.0 MB link
— SRR4175322_GSM2292518 RIP-Seq 111.0 MB link
— SRR4175323_GSM2292519 RIP-Seq 340.0 MB link
— SRR4175324_GSM2292520 RIP-Seq link
— SRR4175325_GSM2292520 RIP-Seq link
— SRR4175326_GSM2292521 RIP-Seq 446.0 MB link