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Title: Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain
Authors: Takeuchi, Akihide  kyouindb  KAKEN_id
Iida, Kei  kyouindb  KAKEN_id  orcid (unconfirmed)
Tsubota, Toshiaki
Hosokawa, Motoyasu
Denawa, Masatsugu
Brown, J.B.
Ninomiya, Kensuke
Ito, Mikako
Kimura, Hiroshi
Abe, Takaya
Kiyonari, Hiroshi
Ohno, Kinji
Hagiwara, Masatoshi  kyouindb  KAKEN_id
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 (
DOI(Published Version): 10.1016/j.celrep.2018.03.141
PubMed ID: 29719248
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