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

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...

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Autores principales: Nelson, Jonathan O, Moore, Kristin A, Chapin, Alex, Hollien, Julie, Metzstein, Mark M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Cell Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848089/
https://www.ncbi.nlm.nih.gov/pubmed/26952209
http://dx.doi.org/10.7554/eLife.12876
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author Nelson, Jonathan O
Moore, Kristin A
Chapin, Alex
Hollien, Julie
Metzstein, Mark M
author_facet Nelson, Jonathan O
Moore, Kristin A
Chapin, Alex
Hollien, Julie
Metzstein, Mark M
author_sort Nelson, Jonathan O
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.12876.001
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spelling pubmed-48480892016-04-29 Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability Nelson, Jonathan O Moore, Kristin A Chapin, Alex Hollien, Julie Metzstein, Mark M eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.12876.001 eLife Sciences Publications, Ltd 2016-03-08 /pmc/articles/PMC4848089/ /pubmed/26952209 http://dx.doi.org/10.7554/eLife.12876 Text en © 2016, Nelson et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Nelson, Jonathan O
Moore, Kristin A
Chapin, Alex
Hollien, Julie
Metzstein, Mark M
Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
title Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
title_full Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
title_fullStr Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
title_full_unstemmed Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
title_short Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
title_sort degradation of gadd45 mrna by nonsense-mediated decay is essential for viability
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848089/
https://www.ncbi.nlm.nih.gov/pubmed/26952209
http://dx.doi.org/10.7554/eLife.12876
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