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Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability

  1. Jonathan O Nelson
  2. Kristin A Moore
  3. Alex Chapin
  4. Julie Hollien
  5. Mark M Metzstein  Is a corresponding author
  1. University of Utah, United States
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Cite this article as: eLife 2016;5:e12876 doi: 10.7554/eLife.12876

Abstract

The nonsense-mediated mRNA decay (NMD) pathway functions to degrade both abnormal and wild-type mRNAs. NMD is essential for viability in most organisms, but the molecular basis for this requirement is unknown. Here we show that a single, conserved NMD target, the mRNA coding for the stress response factor Growth arrest and DNA-damage inducible 45 (GADD45) can account for lethality in Drosophila lacking core NMD genes. Moreover, depletion of Gadd45 in mammalian cells rescues the cell survival defects associated with NMD knockdown. Our findings demonstrate that degradation of Gadd45 mRNA is the essential NMD function and, surprisingly, that the surveillance of abnormal mRNAs by this pathway is not necessarily required for viability.

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Author details

  1. Jonathan O Nelson

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kristin A Moore

    Department of Biology and the Center for Cell and Genome Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alex Chapin

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Julie Hollien

    Department of Biology and the Center for Cell and Genome Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mark M Metzstein

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    For correspondence
    markm@genetics.utah.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Torben Heick Jensen, Aarhus University, Denmark

Publication history

  1. Received: November 6, 2015
  2. Accepted: March 8, 2016
  3. Accepted Manuscript published: March 8, 2016 (version 1)
  4. Version of Record published: April 27, 2016 (version 2)

Copyright

© 2016, Nelson 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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