Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay.
Nucleic Acids Res
; 48(18): 10259-10279, 2020 10 09.
Article
em En
| MEDLINE
| ID: mdl-32941650
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Códon de Terminação
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Transportadores de Cassetes de Ligação de ATP
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Telomerase
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Degradação do RNAm Mediada por Códon sem Sentido
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article