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

Elife. 2016 Mar 8;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.

Keywords: d. melanogaster; NMD; cell biology; drosophila; gadd45; mRNA decay; upf1; upf2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • Drosophila
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Nonsense Mediated mRNA Decay*

Substances

  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins