Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish.
Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish.
复制标题
DOI：
10.1093/nar/gkq1319
复制
发表时间：
2011-05
影响因子：
14.9
通讯作者：
Cáceres JF
中科院分区：
文献类型：
--
作者：
Anastasaki C;Longman D;Capper A;Patton EE;Cáceres JF
无义介导的mRNA衰变（NMD）途径是存在于所有真核生物中的高度保守的监视机制。它通过选择性降解携带提前终止密码子（PTC）的mRNA来阻止截短蛋白的合成。核心NMD效应子最初是在酿酒酵母和线虫线虫中的遗传筛选中鉴定的，随后通过在其他后生动物中的同源性搜索鉴定的。C.全基因组RNA干扰筛选结果鉴定了两个新的NMD基因，它们对正常的胚胎发育是必需的。他们的人类直系同源物DHX 34和NAG/NBAS是人类细胞中NMD所必需的。在这里，我们发现斑马鱼基因组编码DHX 34和NAG/NBAS的直系同源物。我们发现，吗啉诱导的斑马鱼Dhx 34和Nbas蛋白的耗竭导致严重的发育缺陷和胚胎活力降低。我们还发现Dhx 34和Nbas是斑马鱼胚胎中降解含PTC的mRNA所必需的。在Dhx 34和Nbas morphants中观察到的表型与Upf 1，Smg-5-或Smg-6-耗尽胚胎中的缺陷相似，表明这些因素影响相同的途径，并证实斑马鱼胚胎发生需要主动NMD途径。
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.
登录
查看更多内容
影响因子：
14.9
作者：
Fuller-Pace FV
通讯作者：
Fuller-Pace FV
影响因子：
16.8
作者：
Bühler, M;Steiner, S;Mühlemann, O
通讯作者：
Mühlemann, O
影响因子：
10.5
作者：
LEEDS, P;PELTZ, SW;CULBERTSON, MR
通讯作者：
CULBERTSON, MR
影响因子：
11.4
作者：
Behm-Ansmant, Isabelle;Gatfield, David;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa
影响因子：
16.8
作者：
Kaygun, H;Marzluff, WF
通讯作者：
Marzluff, WF