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Published on: May 13, 2019
The role of Mediator and Little Elongation Complex in transcription termination
Hidehisa Takahashi1, Amol Ranjan2, Shiyuan Chen2
1Department 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.
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.
Insights
Human Mediator subunit MED26 recruits the Little Elongation Complex (LEC) to control transcription termination for non-polyadenylated transcripts, including snRNAs and histone mRNAs, at Cajal bodies.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- The Mediator complex is crucial for RNA Polymerase II transcription.
- MED26, a human Mediator subunit, was previously shown to recruit the Super Elongation Complex (SEC) or Little Elongation Complex (LEC).
- The precise mechanisms by which MED26 engages SEC or LEC for distinct gene regulation remained unclear.
Purpose of the Study:
- To elucidate the role of MED26 in recruiting LEC.
- To investigate how MED26-recruited LEC modulates transcription termination.
- To understand the involvement of MED26-LEC interactions in processing non-polyadenylated transcripts.
Main Methods:
- Investigated MED26's interaction with LEC.
- Analyzed transcription termination of snRNA and RDH genes.
- Examined interactions with transcription factors like CBC-ARS2, NELF/DSIF, Integrator, and Heat Labile Factor.
Main Results:
- MED26 recruits LEC to Cajal bodies to regulate transcription termination of non-polyadenylated transcripts (snRNAs, RDH mRNAs).
- LEC, recruited by MED26, enhances Pol II transcription termination via interaction with CBC-ARS2 and NELF/DSIF.
- MED26-recruited LEC promotes 3' end processing by recruiting Integrator or Heat Labile Factor for snRNA or RDH genes, respectively.
Conclusions:
- MED26 plays a key role in transcription termination of specific non-polyadenylated RNAs through LEC recruitment.
- This mechanism involves interactions with multiple transcription and processing factors at Cajal bodies.
- Findings reveal a novel function of MED26 in precise gene expression regulation.
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