Nonsense-mediated mRNA decay in Drosophila:: at the intersection of the yeast and mammalian pathways
Nonsense-mediated mRNA decay in Drosophila:: at the intersection of the yeast and mammalian pathways
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DOI：
10.1093/emboj/cdg371
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发表时间：
2003-08-01
期刊：
影响因子：
11.4
通讯作者：
Izaurralde, E
中科院分区：
文献类型：
--
作者：
Gatfield, D;Unterholzner, L;Izaurralde, E
无义介导的mRNA衰变（NMD）途径促进含有过早终止密码子（PTC）的mRNA的快速降解。在秀丽隐杆线虫中，已经鉴定了七个在NMD中起重要作用的基因（smg 1 -7）。只有SMG 2 -4（称为UPF 1 -3）在酿酒酵母中具有直系同源物。在这里，我们表明，果蝇直系同源的UPF 1 -3，SMG 1，SMG 5和SMG 6所需的PTC-含有mRNA的降解，但没有SMG 7直系同源在这种生物体。相比之下，SMG 5 -7的直系同源物由人类基因组编码，并且所有三个都是NMD所需的。在人类细胞中，外显子边界已被证明在定义PTC中起关键作用。这种作用是由外显子连接复合物（EJC）的组分介导的。然而，与预期相反的是，我们发现EJC的成分在果蝇细胞中对NMD是不敏感的。因此，PTC定义在果蝇中独立于外显子边界发生。我们的研究结果表明，尽管保守的NMD机制，不同的机制已经发展到区分过早的自然终止密码子在后生动物。
The nonsense-mediated mRNA decay (NMD) pathway promotes the rapid degradation of mRNAs containing premature stop codons (PTCs). In Caenorhabditis elegans, seven genes (smg1-7) playing an essential role in NMD have been identified. Only SMG2-4 (known as UPF1-3) have orthologs in Saccharomyces cerevisiae. Here we show that the Drosophila orthologs of UPF1-3, SMG1, SMG5 and SMG6 are required for the degradation of PTC-containing mRNAs, but that there is no SMG7 ortholog in this organism. In contrast, orthologs of SMG5-7 are encoded by the human genome and all three are required for NMD. In human cells, exon boundaries have been shown to play a critical role in defining PTCs. This role is mediated by components of the exon junction complex (EJC). Contrary to expectation, however, we show that the components of the EJC are dispensable for NMD in Drosophila cells. Consistently, PTC definition occurs independently of exon boundaries in Drosophila. Our findings reveal that despite conservation of the NMD machinery, different mechanisms have evolved to discriminate premature from natural stop codons in metazoa.