Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon
Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon
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DOI：
10.1016/s0092-8674(00)00214-2
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发表时间：
2000-12-22
期刊：
影响因子：
64.5
通讯作者：
Steitz, JA
中科院分区：
文献类型：
--
作者：
Lykke-Andersen, J;Shu, MD;Steitz, JA
无义介导的衰变（NMD）使真核细胞去除含有提前终止密码子的异常mRNA。这些通过下游顺式元件（例如外显子-外显子连接）与真正的终止密码子区分开。我们描述了三种新的人类蛋白质参与NMD，hUpf 2，hUpf 3a，和hUpf 3b。在HeLa细胞提取物中，这些蛋白质与hUpf 1复合，而在完整细胞中，hUpf 3a和hUpf 3b是核质穿梭蛋白，hUpf 2是核周蛋白，hUpf 1是胞质蛋白。hUpf 3a和hUpf 3b在体内选择性地与剪接的β-珠蛋白mRNA结合，并且任何hUpf蛋白质与β-珠蛋白mRNA的3 'UTR的连接都会引起NMD。这些数据表明，动态hUpf复合物的组装在mRNA外显子-外显子连接处的细胞核中起始，并且当在翻译终止位点的下游被识别时在细胞质中触发NMD。
Nonsense-mediated decay (NMD) rids eukaryotic cells of aberrant mRNAs containing premature termination codons. These are discriminated from true termination codons by downstream cis-elements, such as exon-exon junctions. We describe three novel human proteins involved in NMD, hUpf2, hUpf3a, and hUpf3b. While in HeLa cell extracts these proteins are complexed with hUpf1, in intact cells hUpf3a and hUpf3b are nucleocytoplasmic shuttling proteins, hUpf2 is perinuclear, and hUpf1 cytoplasmic. hUpf3a and hUpf3b associate selectively with spliced beta -globin mRNA in vivo, and tethering of any hUpf protein to the 3'UTR of beta -globin mRNA elicits NMD. These data suggest that assembly of a dynamic hUpf complex initiates in the nucleus at mRNA exon-exon junctions and triggers NMD in the cytoplasm when recognized downstream of a translation termination site.