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Title: | Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain |
Authors: | Takeuchi, Akihide Iida, Kei https://orcid.org/0000-0001-7130-8705 (unconfirmed) Tsubota, Toshiaki Hosokawa, Motoyasu Denawa, Masatsugu Brown, J.B. Ninomiya, Kensuke Ito, Mikako Kimura, Hiroshi Abe, Takaya Kiyonari, Hiroshi Ohno, Kinji Hagiwara, Masatoshi |
Author's alias: | 武内, 章英 飯田, 慶 坪田, 智明 細川, 元靖 出縄, 政嗣 二宮, 賢介 伊藤, 美佳子 木村, 宏 阿部, 高也 清成, 寛 大野, 欽司 萩原, 正敏 |
Keywords: | RNA-binding protein transcriptional regulation RNA polymerase II cyclin-dependent kinase 9 RBP/transcript-dependent elongation long-gene transcriptotherapy neuronal development neurological and psychiatric diseases long-gene diseases long genopathies |
Issue Date: | 1-May-2018 |
Publisher: | Elsevier BV |
Journal title: | Cell Reports |
Volume: | 23 |
Issue: | 5 |
Start page: | 1326 |
End page: | 1341 |
Abstract: | Genes specifically expressed in neurons contain members with extended long introns. Longer genes present a problem with respect to fulfilment of gene length transcription, and evidence suggests that dysregulation of long genes is a mechanism underlying neurodegenerative and psychiatric disorders. Here, we report the discovery that RNA-binding protein Sfpq is a critical factor for maintaining transcriptional elongation of long genes. We demonstrate that Sfpq co-transcriptionally binds to long introns and is required for sustaining long-gene transcription by RNA polymerase II through mediating the interaction of cyclin-dependent kinase 9 with the elongation complex. Phenotypically, Sfpq disruption caused neuronal apoptosis in developing mouse brains. Expression analysis of Sfpq-regulated genes revealed specific downregulation of developmentally essential neuronal genes longer than 100 kb in Sfpq-disrupted brains; those genes are enriched in associations with neurodegenerative and psychiatric diseases. The identified molecular machinery yields directions for targeted investigations of the association between long-gene transcriptopathy and neuronal diseases. |
Description: | 神経巨大遺伝子の発現制御メカニズムの発見 --神経難病および精神疾患の病因解明と治療法開発に期待--. 京都大学プレスリリース. 2018-05-02. |
Rights: | © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/2433/230954 |
DOI(Published Version): | 10.1016/j.celrep.2018.03.141 |
PubMed ID: | 29719248 |
Related Link: | https://www.kyoto-u.ac.jp/ja/research-news/2018-05-02-0 |
Appears in Collections: | Journal Articles |
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