1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression
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ICE1 promotes the link between splicing and nonsense-mediated mRNA decay

Research Article
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Cite this article as: eLife 2018;7:e33178 doi: 10.7554/eLife.33178
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Abstract

The nonsense-mediated mRNA decay (NMD) pathway detects aberrant transcripts containing premature termination codons (PTCs) and regulates expression of 5-10% of non-aberrant human mRNAs. To date, most proteins involved in NMD have been identified by genetic screens in model organisms; however, the increased complexity of gene expression regulation in human cells suggests that additional proteins may participate in the human NMD pathway. To identify proteins required for NMD, we performed a genome-wide RNAi screen against >21,000 genes. Canonical members of the NMD pathway were highly enriched as top hits in the siRNA screen, along with numerous candidate NMD factors, including the conserved ICE1/KIAA0947 protein. RNAseq studies reveal that depletion of ICE1 globally enhances accumulation and stability of NMD-target mRNAs. Further, our data suggest that ICE1 uses a putative MIF4G domain to interact with exon junction complex (EJC) proteins and promotes the association of the NMD protein UPF3B with the EJC.

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Article and author information

Author details

  1. Thomas D Baird

    Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ken Chih-Chien Cheng

    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yu-Chi Chen

    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eugen Buehler

    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Scott E Martin

    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. James Inglese

    National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7332-5717
  7. J Robert Hogg

    Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    j.hogg@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5729-5135

Funding

National Heart, Lung, and Blood Institute (Intramural Research Program)

  • Thomas D Baird
  • J Robert Hogg

National Center for Advancing Translational Sciences (Intramural Research Program)

  • Ken Chih-Chien Cheng
  • Yu-Chi Chen
  • Eugen Buehler
  • Scott E Martin
  • James Inglese

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

Reviewing Editor

  1. Rachel Green, Johns Hopkins School of Medicine, United States

Publication history

  1. Received: October 27, 2017
  2. Accepted: March 9, 2018
  3. Accepted Manuscript published: March 12, 2018 (version 1)
  4. Version of Record published: April 9, 2018 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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