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Title: HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_Stress]      
keywords:
Transcriptome or Gene expression
ID:
PRJNA341996
description:
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: Microarray in human iPSC-MNs from patients with hnRNP A2/B1 D290V, VCP R155H, mutations or controls. Samples treated with puromycin or saline. 3 replicates per condition.
accesstypes:
download
landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA341996
authentication:
none
authorization:
none
ID:
pmid:27773581
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R35 GM118069/GM/NIGMS NIH HHS/United States

  • U54 HG007005/HG/NHGRI NIH HHS/United States

  • T32 GM087237/GM/NIGMS NIH HHS/United States

  • R01 HG004659/HG/NHGRI NIH HHS/United States

  • R35 NS097974/NS/NINDS NIH HHS/United States

  • T32 GM008666/GM/NIGMS NIH HHS/United States

  • U54 NS091046/NS/NINDS NIH HHS/United States

  • R01 NS075449/NS/NINDS NIH HHS/United States

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