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Nat Commun. 2020 Feb 26;11(1):1063. doi: 10.1038/s41467-020-14849-1.

The role of Mediator and Little Elongation Complex in transcription termination.

Author information

1
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa, 216-0004, Japan. hide0213@yokohama-cu.ac.jp.
2
Stowers Institute for Medical Research, 1000E 50th Street, Kansas City, MO, 64110, USA.
3
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa, 216-0004, Japan.
4
Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
5
Graduate School of Information Science and Technology, Hokkaido University, Kita 14, Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0814, Japan.
6
Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka, 820-8502, Japan.
7
Department of Nanoparticle Translational Research Tokyo Medical University, 6-7-1, Nishi-Shinjuku, Tokyo, Shinjuku-ku, 160-0023, Japan.
8
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Kanagawa, 226-8501, Japan.
9
Laboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba, 277-8562, Japan.
10
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.
11
Division of Proteomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.
12
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
13
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
14
Stowers Institute for Medical Research, 1000E 50th Street, Kansas City, MO, 64110, USA. JLC@stowers.org.
15
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA. JLC@stowers.org.
16
Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. hatas@med.hokudai.ac.jp.

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.

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