Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay.
Détails
Etat: Public
Version: Final published version
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_52D22787E24C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay.
Périodique
Nucleic acids research
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Statut éditorial
Publié
Date de publication
09/10/2020
Peer-reviewed
Oui
Volume
48
Numéro
18
Pages
10259-10279
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
To gain insight into the mechanistic link between translation termination and nonsense-mediated mRNA decay (NMD), we depleted the ribosome recycling factor ABCE1 in human cells, resulting in an upregulation of NMD-sensitive mRNAs. Suppression of NMD on these mRNAs occurs prior to their SMG6-mediated endonucleolytic cleavage. ABCE1 depletion caused ribosome stalling at termination codons (TCs) and increased ribosome occupancy in 3' UTRs, implying enhanced TC readthrough. ABCE1 knockdown indeed increased the rate of readthrough and continuation of translation in different reading frames, providing a possible explanation for the observed NMD inhibition, since enhanced readthrough displaces NMD activating proteins from the 3' UTR. Our results indicate that stalling at TCs triggers ribosome collisions and activates ribosome quality control. Collectively, we show that improper translation termination can lead to readthrough of the TC, presumably due to ribosome collisions pushing the stalled ribosomes into the 3' UTR, where it can resume translation in-frame as well as out-of-frame.
Mots-clé
3' Untranslated Regions/genetics, ATP-Binding Cassette Transporters/genetics, Codon, Terminator/genetics, Frameshifting, Ribosomal/genetics, Humans, Nonsense Mediated mRNA Decay/genetics, Protein Biosynthesis/genetics, RNA, Messenger/genetics, Ribosomes/genetics, Telomerase/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/09/2020 12:20
Dernière modification de la notice
09/08/2024 14:59