1. Chromosomes and Gene Expression
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ZC3H4 restricts non-coding transcription in human cells

  1. Chris Estell
  2. Lee Davidson
  3. Pieter C Steketee
  4. Adam Monier
  5. Steven West  Is a corresponding author
  1. University of Exeter, United Kingdom
  2. Edinburgh University, United Kingdom
Research Article
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Cite this article as: eLife 2021;10:e67305 doi: 10.7554/eLife.67305

Abstract

The human genome encodes thousands of non-coding RNAs. Many of these terminate early and are then rapidly degraded, but how their transcription is restricted is poorly understood. In a screen for protein-coding gene transcriptional termination factors, we identified ZC3H4. Its depletion causes upregulation and extension of hundreds of unstable transcripts, particularly antisense RNAs and those transcribed from so-called super-enhancers. These loci are occupied by ZC3H4, suggesting that it directly functions in their transcription. Consistently, engineered tethering of ZC3H4 to reporter RNA promotes its degradation by the exosome. ZC3H4 is predominantly metazoan - interesting when considering its impact on enhancer RNAs that are less prominent in single-celled organisms. Finally, ZC3H4 loss causes a substantial reduction in cell proliferation, highlighting its overall importance. In summary, we identify ZC3H4 as playing an important role in restricting non-coding transcription in multi-cellular organisms.

Data availability

Sequencing data have been deposited in GEO under accession code GSE163015. All data generated or analysed during this study are included in the manuscript and supporting files. We include full excel spreadsheets representing gene lists and original mass spectrometry data.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Chris Estell

    Living Systems Institute, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Lee Davidson

    Living Systems Institute, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Pieter C Steketee

    The Royal (Dick) School of Veterinary Studies, Edinburgh University, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Adam Monier

    Living Systems Institute, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Steven West

    Living Systems Institute, University of Exeter, Exeter, United Kingdom
    For correspondence
    S.West@exeter.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7622-9050

Funding

Lister Institute of Preventive Medicine (N/A)

  • Steven West

Wellcome Trust (WT107791/Z/15/Z)

  • Steven West

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Torben Heick Jensen, Aarhus University, Denmark

Publication history

  1. Received: February 7, 2021
  2. Accepted: April 27, 2021
  3. Accepted Manuscript published: April 29, 2021 (version 1)

Copyright

© 2021, Estell et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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