Y14 and hUpf3b form an NMD-activating complex

被引：242

作者：

Gehring, NH

Neu-Yilik, G

Schell, T

Hentze, MW

Kulozik, AE ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Pediat Oncol Hematol & Immunol, D-6900 Heidelberg, Germany

[2] Mol Med Partnership Unit, D-69120 Heidelberg, Germany

[3] European Mol Biol Lab, D-69120 Heidelberg, Germany

来源：

MOLECULAR CELL | 2003年 / 11卷 / 04期

关键词：

D O I：

10.1016/S1097-2765(03)00142-4

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：

Messenger RNAs with premature translation termination codons (PTCs) are degraded by nonsense-mediated mRNA decay (NMD). In mammals, PTCs are discriminated from physiological stop codons by a process thought to involve the splicing-dependent deposition of an exon junction complex (EJC), EJC-mediated recruitment of Upf3, and Upf2 binding to the N terminus of Upf3. Here, we identify a conserved domain of hUpf3b that mediates an interaction with the EJC protein Y14. Tethered function analysis shows that the Y14/hUpf3b interaction is essential for NMD, while surprisingly the interaction between hUpf3b and hUpf2 is not. Nonetheless, hUpf2 is necessary for NMD mediated by tethered Y14. RNAi-induced knockdown and Y14 repletion of siRNA-treated cells implicates Y14 in the degradation of beta-globin NS39 mRNA and demonstrates that Y14 is required for NMD induced by tethered hUpf3b. These results uncover a direct role of Y14 in NMD and suggest an unexpected hierarchy in the assembly of NMD complexes.

引用

页码：939 / 949

页数：11

共 52 条

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