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Aberrant cytoplasmic intron retention is a blueprint for RNA binding protein mislocalization in VCP-related amyotrophic lateral sclerosis
https://oist.repo.nii.ac.jp/records/2366
https://oist.repo.nii.ac.jp/records/23669c2437bd-477b-4110-b561-952c656901d7
名前 / ファイル | ライセンス | アクション |
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Tyzack-2021-Aberrant cytoplasmic intron retent (765.9 kB)
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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 | 2021-11-17 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Aberrant cytoplasmic intron retention is a blueprint for RNA binding protein mislocalization in VCP-related amyotrophic lateral sclerosis | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | cytoplasmic intron retention | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | human stem cell model | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | nuclear/cytoplasmic fractionation | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | amyotrophic lateral sclerosis | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | protein mislocalization | |||||
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) |
Tyzack, Giulia E
× Tyzack, Giulia E× Neeves, Jacob× Crerar, Hamish× Klein, Pierre× Ziff, Oliver× Taha, Doaa M× Luisier, Raphaëlle× Luscombe, Nicholas M× Patani, Rickie |
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書誌情報 |
en : Brain 巻 144, 号 7, p. 1985-1993, 発行日 2021-03-09 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | We recently described aberrantly increased cytoplasmic SFPQ intron-retaining transcripts (IRTs) and concurrent SFPQ protein mislocalization as new hallmarks of amyotrophic lateral sclerosis (ALS). However, the generalizability and potential roles of cytoplasmic IRTs in health and disease remain unclear. Here, using time-resolved deep sequencing of nuclear and cytoplasmic fractions of human induced pluripotent stem cells undergoing motor neurogenesis, we reveal that ALS-causing VCP gene mutations lead to compartment-specific aberrant accumulation of IRTs. Specifically, we identify > 100 IRTs with increased cytoplasmic abundance in ALS samples. Furthermore, these aberrant cytoplasmic IRTs possess sequence-specific attributes and differential predicted binding affinity to RNA binding proteins. Remarkably, TDP-43, SFPQ and FUS-RNA binding proteins known for nuclear-to-cytoplasmic mislocalization in ALS-abundantly and specifically bind to this aberrant cytoplasmic pool of IRTs. Our data are therefore consistent with a novel role for cytoplasmic IRTs in regulating compartment-specific protein abundance. This study provides new molecular insight into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets. | |||||
出版者 | ||||||
出版者 | Oxford University Press on behalf of the Guarantors of Brain. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0006-8950 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1460-2156 | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/33693641 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1093/brain/awab078 | |||||
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/brain/article/144/7/1985/6164957 | |||||
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 |