A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay.

Détails

ID Serval
serval:BIB_5C1B7319BEA4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay.
Périodique
EMBO Journal
Auteur⸱e⸱s
Behm-Ansmant I., Gatfield D., Rehwinkel J., Hilgers V., Izaurralde E.
ISSN
0261-4189 (Print)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
2007
Volume
26
Numéro
6
Pages
1591-1601
Langue
anglais
Résumé
The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs with premature translation termination codons (PTCs). The mechanisms by which PTCs and natural stop codons are discriminated remain unclear. We show that the position of stops relative to the poly(A) tail (and thus of PABPC1) is a critical determinant for PTC definition in Drosophila melanogaster. Indeed, tethering of PABPC1 downstream of a PTC abolishes NMD. Conversely, natural stops trigger NMD when the length of the 3' UTR is increased. However, many endogenous transcripts with exceptionally long 3' UTRs escape NMD, suggesting that the increase in 3' UTR length has co-evolved with the acquisition of features that suppress NMD. We provide evidence for the existence of 3' UTRs conferring immunity to NMD. We also show that PABPC1 binding is sufficient for PTC recognition, regardless of cleavage or polyadenylation. The role of PABPC1 in NMD must go beyond that of providing positional information for PTC definition, because its depletion suppresses NMD under conditions in which translation efficiency is not affected. These findings reveal a conserved role for PABPC1 in mRNA surveillance.
Mots-clé
3' Untranslated Regions/genetics, 3' Untranslated Regions/metabolism, Animals, Blotting, Northern, Blotting, Western, Cell Line, Codon, Nonsense/genetics, Drosophila melanogaster/genetics, Drosophila melanogaster/metabolism, Poly(A)-Binding Protein I/metabolism, RNA Interference, RNA Stability/genetics, RNA Stability/physiology, RNA, Messenger/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/12/2012 11:24
Dernière modification de la notice
20/08/2019 14:14
Données d'usage