PUBLICATION

Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish

Authors
Anastasaki, C., Longman, D., Capper, A., Patton, E.E., and Cáceres, J.F.
ID
ZDB-PUB-110119-26
Date
2011
Source
Nucleic acids research   39(9): 3686-3694 (Journal)
Registered Authors
Patton, E. Elizabeth
Keywords
none
MeSH Terms
  • Animals
  • Codon, Nonsense*
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/genetics*
  • Humans
  • Neoplasm Proteins/metabolism
  • RNA Helicases/genetics
  • RNA Helicases/metabolism
  • RNA Helicases/physiology*
  • RNA Stability*
  • RNA, Messenger/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
21227923 Full text @ Nucleic Acids Res.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping