The role of Mediator and Little Elongation Complex in transcription termination

Hidehisa Takahashi; Amol Ranjan; Shiyuan Chen; Hidefumi Suzuki; Mio Shibata; Tomonori Hirose; Hiroko Hirose; Kazunori Sasaki; Ryota Abe; Kai Chen; Yanfeng He; Ying Zhang; Ichigaku Takigawa; Tadasuke Tsukiyama; Masashi Watanabe; Satoshi Fujii; Midori Iida; Junichi Yamamoto; Yuki Yamaguchi; Yutaka Suzuki; Masaki Matsumoto; Keiichi I. Nakayama; Michael P. Washburn; Anita Saraf; Laurence Florens; Shigeo Sato; Chieri Tomomori-Sato; Ronald C. Conaway; Joan W. Conaway; Shigetsugu Hatakeyama

doi:10.1038/s41467-020-14849-1

The role of Mediator and Little Elongation Complex in transcription termination

Hidehisa Takahashi, Amol Ranjan, Shiyuan Chen, Hidefumi Suzuki, Mio Shibata, Tomonori Hirose, Hiroko Hirose, Kazunori Sasaki, Ryota Abe, Kai Chen, Yanfeng He, Ying Zhang, Ichigaku Takigawa, Tadasuke Tsukiyama, Masashi Watanabe, Satoshi Fujii, Midori Iida, Junichi Yamamoto, Yuki Yamaguchi, Yutaka SuzukiMasaki Matsumoto, Keiichi I. Nakayama, Michael P. Washburn, Anita Saraf, Laurence Florens, Shigeo Sato, Chieri Tomomori-Sato, Ronald C. Conaway, Joan W. Conaway, Shigetsugu Hatakeyama

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Abstract

Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3′ end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

Original language	English (US)
Article number	1063
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-14849-1
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-020-14849-1

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Takahashi, H., Ranjan, A., Chen, S., Suzuki, H., Shibata, M., Hirose, T., Hirose, H., Sasaki, K., Abe, R., Chen, K., He, Y., Zhang, Y., Takigawa, I., Tsukiyama, T., Watanabe, M., Fujii, S., Iida, M., Yamamoto, J., Yamaguchi, Y., ... Hatakeyama, S. (2020). The role of Mediator and Little Elongation Complex in transcription termination. Nature communications, 11(1), Article 1063. https://doi.org/10.1038/s41467-020-14849-1

Takahashi, H, Ranjan, A, Chen, S, Suzuki, H, Shibata, M, Hirose, T, Hirose, H, Sasaki, K, Abe, R, Chen, K, He, Y, Zhang, Y, Takigawa, I, Tsukiyama, T, Watanabe, M, Fujii, S, Iida, M, Yamamoto, J, Yamaguchi, Y, Suzuki, Y, Matsumoto, M, Nakayama, KI, Washburn, MP, Saraf, A, Florens, L, Sato, S, Tomomori-Sato, C, Conaway, RC, Conaway, JW & Hatakeyama, S 2020, 'The role of Mediator and Little Elongation Complex in transcription termination', Nature communications, vol. 11, no. 1, 1063. https://doi.org/10.1038/s41467-020-14849-1

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title = "The role of Mediator and Little Elongation Complex in transcription termination",

abstract = "Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3′ end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.",

author = "Hidehisa Takahashi and Amol Ranjan and Shiyuan Chen and Hidefumi Suzuki and Mio Shibata and Tomonori Hirose and Hiroko Hirose and Kazunori Sasaki and Ryota Abe and Kai Chen and Yanfeng He and Ying Zhang and Ichigaku Takigawa and Tadasuke Tsukiyama and Masashi Watanabe and Satoshi Fujii and Midori Iida and Junichi Yamamoto and Yuki Yamaguchi and Yutaka Suzuki and Masaki Matsumoto and Nakayama, {Keiichi I.} and Washburn, {Michael P.} and Anita Saraf and Laurence Florens and Shigeo Sato and Chieri Tomomori-Sato and Conaway, {Ronald C.} and Conaway, {Joan W.} and Shigetsugu Hatakeyama",

note = "Funding Information: We thank Miho Uchiumi for help in preparing the manuscript, Hitomi Kurosawa, Nozomi Sakurai, Ami Kosaka, Takahiro Asanuma, and Naoki Takahashi for experimental assistance. We also thank J. Ludovic Croxford, Ph.D., of Edanz Group (www. edanzediting.com/ac) for editing a draft of this manuscript. This work was partly supported by Mizuho Oda and Emiko Koda in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University. This work was supported in part by KAKENHI (15H04690, 18H02607 to S.H., 15H04701, 16H06279, 17K19578, 18H02378, 19K22401, 221S0002, and 16H06279 to H.T.) and by Takeda Science Foundation (H.T.), Suhara Memorial Fund (H.T.), Takamatsu Cancer Research Fund (H.T.), The Ichiro Kanehara Foundation (H.T.), Friends of Leukemia Research Fund (H.T.), Ono Cancer Research Fund (H.T.), Kobayashi Foundation for Cancer Research (H.T.), MSD Life Science Foundation (H.T.), The Naito Foundation (H.T.), The Tokyo Biochemical Research Foundation (H.T.), Yokohama Foundation for　Advancement　 of　Medical　Science (H.T.), The Uehara Memorial Foundation (H.T.), and by a grant from the Helen Nelson Medical Research Fund to the Stowers Institute (J.W.C.). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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doi = "10.1038/s41467-020-14849-1",

language = "English (US)",

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AU - Takahashi, Hidehisa

AU - Ranjan, Amol

AU - Chen, Shiyuan

AU - Suzuki, Hidefumi

AU - Shibata, Mio

AU - Hirose, Tomonori

AU - Hirose, Hiroko

AU - Sasaki, Kazunori

AU - Abe, Ryota

AU - Chen, Kai

AU - He, Yanfeng

AU - Zhang, Ying

AU - Takigawa, Ichigaku

AU - Tsukiyama, Tadasuke

AU - Watanabe, Masashi

AU - Fujii, Satoshi

AU - Iida, Midori

AU - Yamamoto, Junichi

AU - Yamaguchi, Yuki

AU - Suzuki, Yutaka

AU - Matsumoto, Masaki

AU - Nakayama, Keiichi I.

AU - Washburn, Michael P.

AU - Saraf, Anita

AU - Florens, Laurence

AU - Sato, Shigeo

AU - Tomomori-Sato, Chieri

AU - Conaway, Ronald C.

AU - Conaway, Joan W.

AU - Hatakeyama, Shigetsugu

N1 - Funding Information: We thank Miho Uchiumi for help in preparing the manuscript, Hitomi Kurosawa, Nozomi Sakurai, Ami Kosaka, Takahiro Asanuma, and Naoki Takahashi for experimental assistance. We also thank J. Ludovic Croxford, Ph.D., of Edanz Group (www. edanzediting.com/ac) for editing a draft of this manuscript. This work was partly supported by Mizuho Oda and Emiko Koda in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University. This work was supported in part by KAKENHI (15H04690, 18H02607 to S.H., 15H04701, 16H06279, 17K19578, 18H02378, 19K22401, 221S0002, and 16H06279 to H.T.) and by Takeda Science Foundation (H.T.), Suhara Memorial Fund (H.T.), Takamatsu Cancer Research Fund (H.T.), The Ichiro Kanehara Foundation (H.T.), Friends of Leukemia Research Fund (H.T.), Ono Cancer Research Fund (H.T.), Kobayashi Foundation for Cancer Research (H.T.), MSD Life Science Foundation (H.T.), The Naito Foundation (H.T.), The Tokyo Biochemical Research Foundation (H.T.), Yokohama Foundation for　Advancement　 of　Medical　Science (H.T.), The Uehara Memorial Foundation (H.T.), and by a grant from the Helen Nelson Medical Research Fund to the Stowers Institute (J.W.C.). Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3′ end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

AB - Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3′ end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

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The role of Mediator and Little Elongation Complex in transcription termination

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