Y14 and hUpf3b form an NMD-activating complex.
Mol Cell
; 11(4): 939-49, 2003 Apr.
Article
in En
| MEDLINE
| ID: mdl-12718880
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Biosynthesis
/
RNA, Messenger
/
Exons
/
RNA-Binding Proteins
/
Codon, Nonsense
/
Eukaryotic Cells
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2003
Document type:
Article
Affiliation country:
Alemania