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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 20, 2016 |
| Title |
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_small_rnaseq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| 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.
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| Overall design |
small RNA-seq in mouse spinal after injection with ASO against hnRNP A2/B1 or saline. Three or four replicates per condition
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| Contributor(s) |
Martinez FJ, Pratt GA, Van Nostrand E, Batra R, Huelga SC, Kapeli K, Fang M, Freese P, Chun SJ, Gelboin-Burkhart C, Fijany L, Wang H, Nussbacher JK, Kim H, Lardelli R, Tang S, Sundararaman B, Donohue JP, Lykke-Andersen J, Ding S, Ling S, Bennett F, Ares M Jr, Burge CB, Taylor JP, Rigo F, Yeo GW |
| Citation(s) |
27773581 |
| Submission date |
Aug 30, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gene Yeo |
| E-mail(s) |
geneyeo@ucsd.edu
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| Organization name |
UCSD
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| Street address |
2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (2) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE86464 |
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons |
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| Relations |
| BioProject |
PRJNA341998 |
| SRA |
SRP086705 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86227_mature_counts_hg19.csv.gz |
46.1 Kb |
(ftp)(http) |
CSV |
| GSE86227_mature_counts_mm10.csv.gz |
43.3 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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