GSE86227
GSE GEOHNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_small_rnaseq]
Relations
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- Sequencing reads from small RNA-seq libraries were first trimmed adapters using cutadapt
- Reads were then mapped against a database of repetitive elements derived from RepBase18.05.
- 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).
- 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
- counts of reads for each gene annotated in gencode vM3 were calculated from featureCounts for mouse and v19 for human
Supplementary Files (2)
Dataset Citations (1)
SRA Experiments (12) and Runs (12)
Total: 274 MBSample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |