title: Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability.
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.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, United States.
authors.forename: Jonathan O
authors.identifier: 0000-0001-9831-745X
authors.initials: JO
authors.lastname: Nelson
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, United States.|Center for Cell and Genome Sciences, University of Utah, Salt Lake City, United States.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Moore
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Chapin
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, United States.|Center for Cell and Genome Sciences, University of Utah, Salt Lake City, United States.
authors.forename: Julie
authors.initials: J
authors.lastname: Hollien
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, United States.
authors.forename: Mark M
authors.identifier: 0000-0002-4105-2750
authors.initials: MM
authors.lastname: Metzstein
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004330:Drosophila; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D059365:Nonsense Mediated mRNA Decay; D000097642:GADD45 Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000097642:GADD45 Proteins
keywords: <i>d. melanogaster</i>; NMD; cell biology; drosophila; gadd45; mRNA decay; upf1; upf2