TY - JOUR
T1 - Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish
AU - Anastasaki, Corina
AU - Longman, Dasa
AU - Capper, Amy
AU - Patton, E. Elizabeth
AU - Cáceres, Javier F.
N1 - Funding Information:
Medical Research Council (to E.E.P. and J.F.C.); Eurasnet (LSHG-CT-2005-518238) (to J.F.C.); Wellcome Trust (to E.E.P.); European Union FP7 programme ZF-CANCER (to E.E.P); Association for International Cancer Research (to E.E.P.); Medical Research Scotland (to E.E.P.). Funding for open access charge: MRC.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79955954056&partnerID=8YFLogxK
U2 - 10.1093/nar/gkq1319
DO - 10.1093/nar/gkq1319
M3 - Article
C2 - 21227923
AN - SCOPUS:79955954056
SN - 0305-1048
VL - 39
SP - 3686
EP - 3694
JO - Nucleic acids research
JF - Nucleic acids research
IS - 9
ER -