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GSE86227

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_small_rnaseq]

Organism: Mus musculus
Platform: GPL15520
Samples: 12
Experiment Types:
Non-coding RNA profiling by high throughput sequencing
Submitted: Aug 30 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/PRJNA341998 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP086705

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

small RNA-seq in mouse spinal after injection with ASO against hnRNP A2/B1 or saline. Three or four replicates per condition

Analysis (5 steps)

View Data Processing
Processing steps for GSE86227
  1. Sequencing reads from small RNA-seq libraries were first trimmed adapters using cutadapt
  2. Reads were then mapped against a database of repetitive elements derived from RepBase18.05.
  3. Bowtie version 1.0.0 with parameters -S -q -p 16 -e 100 -l 20 was used to align reads against an index generated from Repbase sequences (Langmead et al., 2009).
  4. Reads not mapped to Repbase sequences were aligned to the mm9 or hg19 genome (UCSC assembly) using bowtie version 1.1.1 with parameters -p 8 -k 1 -m 10 -l 25 --best --chunkmbs 128
  5. counts of reads for each gene annotated in gencode vM3 were calculated from featureCounts for mouse and v19 for human

Supplementary Files (2)

GSE86227_mature_counts_hg19.csv.gz Download
GSE86227_mature_counts_mm10.csv.gz Download
GEO Samples (12)

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 (12) and Runs (12)

Total: 274 MB
SRX2140598 SRP086705 ncRNA-Seq SINGLE
GSM2298799: saline control 1 [mouse]; Mus musculus; ncRNA-Seq
Sample: SRS1672521
BioProject: PRJNA341998
BioSample: SAMN05731006
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Mus musculus
Sample attributes
source_name: spinal cord
strain: C57BL/6J
age: 8weeks
tissue type: spinal cord
treatment: saline
Original files (1)
spinal cord
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175377 1415527 50958972 24.51 B7P80-A1_S2_L001_R1_001.fastq, SRR4175377, SRR4175377.sralite SRA
SRX2140599 SRP086705 ncRNA-Seq SINGLE
GSM2298800: saline control 2 [mouse]; Mus musculus; ncRNA-Seq
Sample: SRS1672522
BioProject: PRJNA341998
BioSample: SAMN05731005
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Mus musculus
Sample attributes
source_name: spinal cord
strain: C57BL/6J
age: 8weeks
tissue type: spinal cord
treatment: saline
Original files (1)
spinal cord
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175378 1215467 43756812 21.57 B7P80-A2_S9_L001_R1_001.fastq, SRR4175378, SRR4175378.sralite SRA
SRX2140600 SRP086705 ncRNA-Seq SINGLE
GSM2298801: saline control 3 [mouse]; Mus musculus; ncRNA-Seq
Sample: SRS1672523
BioProject: PRJNA341998
BioSample: SAMN05731000
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Mus musculus
Sample attributes
source_name: spinal cord
strain: C57BL/6J
age: 8weeks
tissue type: spinal cord
treatment: saline
Original files (1)
spinal cord
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175379 1192450 42928200 21.14 B7P80-A3_S11_L001_R1_001.fastq, SRR4175379, SRR4175379.sralite SRA
SRX2140601 SRP086705 ncRNA-Seq SINGLE
GSM2298802: hnRNP A2/B1 ASO 1 [mouse]; Mus musculus; ncRNA-Seq
Sample: SRS1672524
BioProject: PRJNA341998
BioSample: SAMN05730999
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Mus musculus
Sample attributes
source_name: spinal cord
strain: C57BL/6J
age: 8weeks
tissue type: spinal cord
treatment: ASO Hnrnpa2/b1
Original files (1)
spinal cord
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175380 1283095 46191420 22.57 B7P80-D1_S12_L001_R1_001.fastq, SRR4175380, SRR4175380.sralite SRA
SRX2140602 SRP086705 ncRNA-Seq SINGLE
GSM2298803: hnRNP A2/B1 ASO 2 [mouse]; Mus musculus; ncRNA-Seq
Sample: SRS1672525
BioProject: PRJNA341998
BioSample: SAMN05731001
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Mus musculus
Sample attributes
source_name: spinal cord
strain: C57BL/6J
age: 8weeks
tissue type: spinal cord
treatment: ASO Hnrnpa2/b1
Original files (1)
spinal cord
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175381 1160057 41762052 20.32 B7P80-D2_S13_L001_R1_001.fastq, SRR4175381, SRR4175381.sralite SRA
SRX2140603 SRP086705 ncRNA-Seq SINGLE
GSM2298804: hnRNP A2/B1 ASO 3 [mouse]; Mus musculus; ncRNA-Seq
Sample: SRS1672526
BioProject: PRJNA341998
BioSample: SAMN05730998
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Mus musculus
Sample attributes
source_name: spinal cord
strain: C57BL/6J
age: 8weeks
tissue type: spinal cord
treatment: ASO Hnrnpa2/b1
Original files (1)
spinal cord
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175382 2084468 75040848 35.77 B7P80-D3_S8_L001_R1_001.fastq, SRR4175382, SRR4175382.sralite SRA
SRX2140604 SRP086705 ncRNA-Seq SINGLE
GSM2298805: saline control 1 [human]; Homo sapiens; ncRNA-Seq
Sample: SRS1672527
BioProject: PRJNA341998
BioSample: SAMN05730997
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Homo sapiens
Sample attributes
source_name: CVBiPS
cell type: craig venter iPS cells
treatment: saline
Original files (1)
CVBiPS
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175383 1132234 40760424 20.34 B7P80-C-1_S4_L001_R1_001.fastq, SRR4175383, SRR4175383.sralite SRA
SRX2140605 SRP086705 ncRNA-Seq SINGLE
GSM2298806: saline control 2 [human]; Homo sapiens; ncRNA-Seq
Sample: SRS1672528
BioProject: PRJNA341998
BioSample: SAMN05731009
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Homo sapiens
Sample attributes
source_name: CVBiPS
cell type: craig venter iPS cells
treatment: saline
Original files (1)
CVBiPS
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175384 1029699 37069164 18.12 B7P80-C-2_S5_L001_R1_001.fastq, SRR4175384, SRR4175384.sralite SRA
SRX2140606 SRP086705 ncRNA-Seq SINGLE
GSM2298807: saline control 3 [human]; Homo sapiens; ncRNA-Seq
Sample: SRS1672529
BioProject: PRJNA341998
BioSample: SAMN05731008
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Homo sapiens
Sample attributes
source_name: CVBiPS
cell type: craig venter iPS cells
treatment: saline
Original files (1)
CVBiPS
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175385 1194571 43004556 21.17 B7P80-C-3_S6_L001_R1_001.fastq, SRR4175385, SRR4175385.sralite SRA
SRX2140607 SRP086705 ncRNA-Seq SINGLE
GSM2298808: hnRNP A2/B1 ASO 1 [human]; Homo sapiens; ncRNA-Seq
Sample: SRS1672530
BioProject: PRJNA341998
BioSample: SAMN05731007
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Homo sapiens
Sample attributes
source_name: CVBiPS
cell type: craig venter iPS cells
treatment: ASO Hnrnpa2/b1
Original files (1)
CVBiPS
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175386 1510692 54384912 27.57 B7P80-501-1_S7_L001_R1_001.fastq, SRR4175386, SRR4175386.sralite SRA
SRX2140608 SRP086705 ncRNA-Seq SINGLE
GSM2298809: hnRNP A2/B1 ASO 2 [human]; Homo sapiens; ncRNA-Seq
Sample: SRS1672531
BioProject: PRJNA341998
BioSample: SAMN05731004
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Homo sapiens
Sample attributes
source_name: CVBiPS
cell type: craig venter iPS cells
treatment: ASO Hnrnpa2/b1
Original files (1)
CVBiPS
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175387 1177414 42386904 20.91 B7P80-501-2_S1_L001_R1_001.fastq, SRR4175387, SRR4175387.sralite SRA
SRX2140609 SRP086705 ncRNA-Seq SINGLE
GSM2298810: hnRNP A2/B1 ASO 3 [human]; Homo sapiens; ncRNA-Seq
Sample: SRS1672532
BioProject: PRJNA341998
BioSample: SAMN05731003
Platform: ILLUMINA
Instrument: Illumina MiSeq
Organism: Homo sapiens
Sample attributes
source_name: CVBiPS
cell type: craig venter iPS cells
treatment: ASO Hnrnpa2/b1
Original files (1)
CVBiPS
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR4175388 1115399 40154364 20.48 B7P80-501-3_S3_L001_R1_001.fastq, SRR4175388, SRR4175388.sralite SRA

Linked Publications (1)

Data Files (24)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
B7P80-501-1_S7_L001_R1_001.fastq ncRNA-Seq 27.6 MB link
B7P80-501-1_S7_L001_R1_001.fastq ncRNA-Seq 27.6 MB link
B7P80-501-2_S1_L001_R1_001.fastq ncRNA-Seq 20.9 MB link
B7P80-501-2_S1_L001_R1_001.fastq ncRNA-Seq 20.9 MB link
B7P80-501-3_S3_L001_R1_001.fastq ncRNA-Seq 20.5 MB link
B7P80-501-3_S3_L001_R1_001.fastq ncRNA-Seq 20.5 MB link
B7P80-A1_S2_L001_R1_001.fastq ncRNA-Seq 24.5 MB link
B7P80-A1_S2_L001_R1_001.fastq ncRNA-Seq 24.5 MB link
B7P80-A2_S9_L001_R1_001.fastq ncRNA-Seq 21.6 MB link
B7P80-A2_S9_L001_R1_001.fastq ncRNA-Seq 21.6 MB link
B7P80-A3_S11_L001_R1_001.fastq ncRNA-Seq 21.1 MB link
B7P80-A3_S11_L001_R1_001.fastq ncRNA-Seq 21.1 MB link
B7P80-C-1_S4_L001_R1_001.fastq ncRNA-Seq 20.3 MB link
B7P80-C-1_S4_L001_R1_001.fastq ncRNA-Seq 20.3 MB link
B7P80-C-2_S5_L001_R1_001.fastq ncRNA-Seq 18.1 MB link
B7P80-C-2_S5_L001_R1_001.fastq ncRNA-Seq 18.1 MB link
B7P80-C-3_S6_L001_R1_001.fastq ncRNA-Seq 21.2 MB link
B7P80-C-3_S6_L001_R1_001.fastq ncRNA-Seq 21.2 MB link
B7P80-D1_S12_L001_R1_001.fastq ncRNA-Seq 22.6 MB link
B7P80-D1_S12_L001_R1_001.fastq ncRNA-Seq 22.6 MB link
B7P80-D2_S13_L001_R1_001.fastq ncRNA-Seq 20.3 MB link
B7P80-D2_S13_L001_R1_001.fastq ncRNA-Seq 20.3 MB link
B7P80-D3_S8_L001_R1_001.fastq ncRNA-Seq 35.8 MB link
B7P80-D3_S8_L001_R1_001.fastq ncRNA-Seq 35.8 MB link