Cleavage of the A Site mRNA Codon during Ribosome Pausing Provides a Mechanism for Translational Quality Control

Cells employ many mechanisms to ensure quality control during protein biosynthesis. Here, we show that, during the pausing of a bacterial ribosome, the mRNA being translated is cleaved at a site within or immediately adjacent to the A site codon. The extent of this A site mRNA cleavage is correlated...

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Veröffentlicht in:Molecular cell 2003-10, Vol.12 (4), p.903-911
Hauptverfasser: Hayes, Christopher S, Sauer, Robert T
Format: Artikel
Sprache:eng
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Zusammenfassung:Cells employ many mechanisms to ensure quality control during protein biosynthesis. Here, we show that, during the pausing of a bacterial ribosome, the mRNA being translated is cleaved at a site within or immediately adjacent to the A site codon. The extent of this A site mRNA cleavage is correlated with the extent of ribosome pausing as assayed by tmRNA-mediated tagging of the nascent polypeptide. Cleavage does not require tmRNA, the ribosomal alarmone (p)ppGpp, or bacterial toxins such as RelE which have been shown to stimulate a similar activity. Translation is required for cleavage, suggesting that the ribosome participates in the reaction in some fashion. When normal protein synthesis is compromised, A site mRNA cleavage and the tmRNA system provide a mechanism for reducing translational errors and the production of aberrant and potentially harmful polypeptides.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(03)00385-X