Y14 and hUpf3b form an NMD-activating complex.

Abstract:

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Gehring NH,Neu-Yilik G,Schell T,Hentze MW,Kulozik AE

doi

10.1016/s1097-2765(03)00142-4

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

939-49

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(03)00142-4

journal_volume

11

pub_type

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