Human THO coordinates transcription termination and subsequent transcript release from the <i>HSP70</i> locus
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- Jun Katahira
- Laboratory of Cellular and Molecular Biology, Department of Veterinary Sciences Osaka Prefecture University Izumisano Osaka Japan
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- Hiroki Ishikawa
- Laboratory of Cellular and Molecular Biology, Department of Veterinary Sciences Osaka Prefecture University Izumisano Osaka Japan
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- Kakeru Tsujimura
- Laboratory of Cellular and Molecular Biology, Department of Veterinary Sciences Osaka Prefecture University Izumisano Osaka Japan
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- Sadamu Kurono
- Graduate School of Medicine and Health Sciences Osaka University Suita Osaka Japan
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- Miki Hieda
- Graduate School of Health Sciences Ehime Prefectural University of Health Sciences Iyo‐gun Ehime Japan
書誌事項
- 公開日
- 2019-02-27
- 資源種別
- journal article
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1111/gtc.12672
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>A multiprotein complex, THO/TREX, couples the transcription, 3′‐end formation and nuclear export of mRNAs. In this study, we report that crucial factors for mRNA processing, such as XRN2, DDX5/DDX17 and CstF64, are copurified with human THO (hTHO). Using chromatin immunoprecipitation, we found increased cross‐linking of XRN2 and CstF64 to the RNA polymerase II (RNAP II) pause site of the <jats:italic>HSPA1A</jats:italic> gene upon down‐regulation of THOC5, a metazoan‐specific component of hTHO. As observed in THOC5‐depleted cells, knockdown of XRN2 blocked <jats:italic>HSP70</jats:italic> transcript release and increased the amount of CstF64 at the pause site. In addition, our data indicate that DDX5/DDX17 is also required for <jats:italic>HSP70</jats:italic> transcript release. As the degradation of read‐through transcripts, but not cleavage at polyadenylation sites per se, was hindered upon THOC5 or DDX5/DDX17 down‐regulation, these factors appear to influence transcriptional termination. Interestingly, over‐expression of RNase H suppressed the accumulation of <jats:italic>HSP70</jats:italic> transcripts in nuclear foci in THOC5‐ or DDX5/DDX17‐depleted cells. Thus, we propose a model in which hTHO, along with DDX5/DDX17, restricts the formation of R‐loops, thereby facilitating the XRN2‐mediated transcriptional termination and release of the mature transcript from the <jats:italic>HSPA1A</jats:italic> locus.</jats:p>
収録刊行物
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- Genes to Cells
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Genes to Cells 24 (4), 272-283, 2019-02-27
Wiley
