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Series GSE86227 Query DataSets for GSE86227
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
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
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
Organization name UCSD
Street address 2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (2)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (12)
GSM2298799 saline control 1 [mouse]
GSM2298800 saline control 2 [mouse]
GSM2298801 saline control 3 [mouse]
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
BioProject PRJNA341998
SRA SRP086705

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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
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Processed data are available on Series record
Raw data are available in SRA

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