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Six GU-rich (6GUR) FUS-binding motifs detected by normalization of CLIP-seq by Nascent-seq
http://hdl.handle.net/2237/26860
http://hdl.handle.net/2237/26860dc173024-4ec7-4d1f-9018-f7c6f8d95c46
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
Preprint_1st_draft.pdf ファイル公開：2018/06/30 (807.9 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-08-02 | |||||
| タイトル | ||||||
| タイトル | Six GU-rich (6GUR) FUS-binding motifs detected by normalization of CLIP-seq by Nascent-seq | |||||
| 言語 | en | |||||
| 著者 |
Takeda, Jun-ichi
× Takeda, Jun-ichi× Masuda, Akio× Ohno, Kinji |
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| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | FUS | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | RNA-binding protein | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | RNA-binding motif | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | CLIP-seq | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Nascent-seq | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | FUS, an RNA-binding protein (RBP), is mutated or abnormally regulated in neurodegenerative disorders. FUS regulates various aspects of RNA metabolisms. FUS binding sites are rich in GU contents and are highly degenerative. FUS-binding motifs of GGU, GGUG, GUGGU and CGCGC have been previously reported. These motifs, however, are applicable to a small fraction of FUS-binding sites. As CLIP-seq tags are enriched in genes that are highly expressed, we normalized CLIP-seq tags by Nascent-seq tags or RNA-seq tags of mouse N2a cells.Nascent-seq identifies nascent transcripts before being processed for splicing and polyadenylation. We extracted frequently observed 4-nt motifs from Nascent-seq normalized CLIP regions, RNA-seq-normalized CLIP regions,and native CLIP regions. Specific GU-rich motifs were best detected in Nascent-seq-normalized CLIP regions. Analysis of structural motifs using Nascent-seq-normalized CLIP regions also predicted GU-rich sequence forming a stem structure. Sensitivity and specificity were calculated by examining whether the extracted motifs were present at the cross-linking-induced mutation sites (CIMS), where FUS was directly bound. We found that a combination of six motifs (UGUG, CUGG, UGGU, GCUG, GUGG, and UUGG), which were extracted from Nascent-seq-normalized CLIP-regions, had a better discriminative power than (i) motifs extracted from RNA-seqnormalized CLIP regions, (ii) motifs extracted from native CLIP regions, (iii) previously reported individual motifs, or (iv) 15 motifs in SpliceAid 2. Validation of the 6 GU-rich (6GUR) motifs using CLIP-seq of the cerebrum and the whole brain showed that the 6GUR motifs were specifically enriched in CIMS. The number of the 6GUR motifs in an uninterrupted region was counted and multiplied by four to calculate the area, which was defined as the 6GUR-Score. The 6GUR-Score of 8 or more best discriminated CIMS from CIMS-flanking regions. We propose that the 6GUR motifs predict FUS-binding sites more efficiently than previously reported individual motifs or 15 motifs in SpliceAid 2. | |||||
| 言語 | en | |||||
| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| 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 | |||||
| 出版タイプ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.gene.2017.04.008 | |||||
| ISSN | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0378-1119 | |||||
| 書誌情報 |
en : Gene 巻 618, p. 57-64, 発行日 2017-06-30 |
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| 著者版フラグ | ||||||
| 値 | author | |||||
| URI | ||||||
| 識別子 | https://doi.org/10.1016/j.gene.2017.04.008 | |||||
| 識別子タイプ | DOI | |||||
| URI | ||||||
| 識別子 | http://hdl.handle.net/2237/26860 | |||||
| 識別子タイプ | HDL | |||||
