Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon

被引：473

作者：

Lykke-Andersen, J ^{[1
]}

Shu, MD ^{[1
]}

Steitz, JA ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, Howard Hughes Med Inst, New Haven, CT 06536 USA

来源：

CELL | 2000年 / 103卷 / 07期

关键词：

D O I：

10.1016/S0092-8674(00)00214-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1121 / 1131

页数：11

共 67 条

[1] Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein [J].