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Widespread FUS mislocalization is a molecular hallmark of amyotrophic lateral sclerosis
https://oist.repo.nii.ac.jp/records/1436
https://oist.repo.nii.ac.jp/records/143658a6412e-4a9a-4999-9f30-bb4097b72573
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
Tyzack-2019-Widespread FUS mislo (1.1 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 | 2020-05-01 | |||||
| タイトル | ||||||
| タイトル | Widespread FUS mislocalization is a molecular hallmark of amyotrophic lateral sclerosis | |||||
| 言語 | en | |||||
| 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） |
Tyzack, Giulia E
× Tyzack, Giulia E× Luisier, Raphaelle× Taha, Doaa M× Neeves, Jacob× Modic, Miha× Mitchell, Jamie S× Meyer, Ione× Greensmith, Linda× Newcombe, Jia× Ule, Jernej× Luscombe, Nicholas M× Patani, Rickie |
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| 書誌情報 |
en : Brain 巻 142, 号 9, p. 2572-2580, 発行日 2019-08-01 |
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| 抄録 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Mutations causing amyotrophic lateral sclerosis (ALS) clearly implicate ubiquitously expressed and predominantly nuclear RNA binding proteins, which form pathological cytoplasmic inclusions in this context. However, the possibility that wild-type RNA binding proteins mislocalize without necessarily becoming constituents of cytoplasmic inclusions themselves remains relatively unexplored. We hypothesized that nuclear-to-cytoplasmic mislocalization of the RNA binding protein fused in sarcoma (FUS), in an unaggregated state, may occur more widely in ALS than previously recognized. To address this hypothesis, we analysed motor neurons from a human ALS induced-pluripotent stem cell model caused by the VCP mutation. Additionally, we examined mouse transgenic models and post-mortem tissue from human sporadic ALS cases. We report nuclear-to-cytoplasmic mislocalization of FUS in both VCP-mutation related ALS and, crucially, in sporadic ALS spinal cord tissue from multiple cases. Furthermore, we provide evidence that FUS protein binds to an aberrantly retained intron within the SFPQ transcript, which is exported from the nucleus into the cytoplasm. Collectively, these data support a model for ALS pathogenesis whereby aberrant intron retention in SFPQ transcripts contributes to FUS mislocalization through their direct interaction and nuclear export. In summary, we report widespread mislocalization of the FUS protein in ALS and propose a putative underlying mechanism for this process. | |||||
| 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/31368485 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1093/brain/awz217 | |||||
| 権利 | ||||||
| 権利情報 | © 2019 The Author(s) | |||||
| 情報源 | ||||||
| 関連名称 | https://creativecommons.org/licenses/by/4.0/ | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://academic.oup.com/brain/article/142/9/2572/5542493 | |||||
| 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 | |||||
