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Reactive astrocytes in ALS display diminished intron retention
https://oist.repo.nii.ac.jp/records/2142
https://oist.repo.nii.ac.jp/records/2142cd61b1d3-1355-44ae-812c-17c25745dfff
名前 / ファイル | ライセンス | アクション |
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Ziff-2021-Reactive astrocytes in ALS display d (6.4 MB)
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Creative Commons Attribution 4.0 International(https://creativecommons.org/licenses/by/4.0/)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-05-28 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Reactive astrocytes in ALS display diminished intron retention | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者(英) |
Ziff, Oliver J
× Ziff, Oliver J× Taha, Doaa M× Crerar, Hamish× Clarke, Benjamin E× Chakrabarti, Anob M× Kelly, Gavin× Neeves, Jacob× Tyzack, Giulia E× Luscombe, Nicholas M× Patani, Rickie |
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書誌情報 |
en : Nucleic Acids Research 巻 49, 号 6, p. 3168-3184, 発行日 2021-03-04 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Reactive astrocytes are implicated in amyotrophic lateral sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human-induced pluripotent stem cell (hiPSC)-derived astrocytes carrying ALS-causing mutations in VCP, SOD1 and C9orf72. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell adhesion, stress response and immune activation. This was recapitulated in public-datasets for (i) hiPSC-derived astrocytes stimulated with cytokines to undergo reactive transformation and (ii) in vivo astrocytes following selective deletion of TDP-43. We also re-examined public translatome sequencing (TRAP-seq) of astrocytes from a SOD1 mouse model, which revealed that transcripts upregulated in translation significantly overlap with transcripts exhibiting decreased IR. Using nucleocytoplasmic fractionation of VCP mutant astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear transcripts is associated with enhanced nonsense mediated decay and increased cytoplasmic expression of transcripts and proteins regulating reactive transformation. These findings are consistent with a molecular model for reactive transformation in astrocytes whereby poised nuclear reactivity-related IR transcripts are spliced, undergo nuclear-to-cytoplasmic translocation and translation. Our study therefore provides new insights into the molecular regulation of reactive transformation in astrocytes. | |||||
出版者 | ||||||
出版者 | Oxford University Press on behalf of Nucleic Acids Research. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0305-1048 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1362-4962 | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/33684213 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1093/nar/gkab115 | |||||
権利 | ||||||
権利情報 | © 2021 The Author(s). | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://academic.oup.com/nar/article/49/6/3168/6155937 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |