An active role for the ribosome in determining the fate of oxidized mRNA.
Cell Rep
; 9(4): 1256-64, 2014 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-25456128
ABSTRACT
Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity of the selection process, suggesting that the modification stalls the translational machinery. Consistent with these findings, 8-oxoG mRNAs were observed to accumulate and associate with polyribosomes in yeast strains in which no-go decay is compromised. Our data provide compelling evidence that mRNA-surveillance mechanisms have evolved to cope with damaged mRNA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ribossomos
/
RNA Mensageiro
/
Guanosina
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article