Sequence selectivity of macrolide-induced translational attenuation

Amber R. Davis, David W. Gohara, Mee-Ngan Frances Yap*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

The prevailing "plug-in-the-bottle" model suggests that macrolide antibiotics inhibit translation by binding inside the ribosome tunnel and indiscriminately arresting the elongation of every nascent polypeptide after the synthesis of six to eight amino acids. To test this model, we performed a genome-wide analysis of translation in azithromycin-treated Staphylococcus aureus. In contrast to earlier predictions, we found that the macrolide does not preferentially induce ribosome stalling near the 5? end of mRNAs, but rather acts at specific stalling sites that are scattered throughout the entire coding region. These sites are highly enriched in prolines and charged residues and are strikingly similar to other ligandindependent ribosome stalling motifs. Interestingly, the addition of structurally related macrolides had dramatically different effects on stalling efficiency. Our data suggest that ribosome stalling can occur at a surprisingly large number of low-complexity motifs in a fashion that depends only on a few arrest-inducing residues and the presence of a small molecule inducer.

Original languageEnglish (US)
Pages (from-to)15379-15384
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number43
DOIs
StatePublished - Oct 28 2014

ASJC Scopus subject areas

  • General

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