title: Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish.
abstract: The nonsense-mediated mRNA decay (NMD) pathway is a highly conserved surveillance mechanism that is present in all eukaryotes. It prevents the synthesis of truncated proteins by selectively degrading mRNAs harbouring premature termination codons (PTCs). The core NMD effectors were originally identified in genetic screens in Saccharomyces cerevisae and in the nematode Caenorhabditis elegans, and subsequently by homology searches in other metazoans. A genome-wide RNAi screen in C. elegans resulted in the identification of two novel NMD genes that are essential for proper embryonic development. Their human orthologues, DHX34 and NAG/NBAS, are required for NMD in human cells. Here, we find that the zebrafish genome encodes orthologues of DHX34 and NAG/NBAS. We show that the morpholino-induced depletion of zebrafish Dhx34 and Nbas proteins results in severe developmental defects and reduced embryonic viability. We also found that Dhx34 and Nbas are required for degradation of PTC-containing mRNAs in zebrafish embryos. The phenotypes observed in both Dhx34 and Nbas morphants are similar to defects in Upf1, Smg-5- or Smg-6- depleted embryos, suggesting that these factors affect the same pathway and confirming that zebrafish embryogenesis requires an active NMD pathway.
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Corina
authors.initials: C
authors.lastname: Anastasaki
authors.forename: Dasa
authors.initials: D
authors.lastname: Longman
authors.forename: Amy
authors.initials: A
authors.lastname: Capper
authors.forename: E Elizabeth
authors.initials: EE
authors.lastname: Patton
authors.forename: Javier F
authors.initials: JF
authors.lastname: Cáceres
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018389:Codon, Nonsense; C117339:NBAS protein, human; C559843:NBAS protein, zebrafish; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C559844:DHX34 protein, human; C559842:DHX34 protein, zebrafish; D020365:RNA Helicases