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Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Koch Miriam , Willi Jessica , Pradère Ugo , Hall Jonathan , Polacek Norbert ,
Project Stress-mediated effects on ribosome functions and translation control
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Original article (peer-reviewed)

Journal Nucleic Acids Research
Page(s) 6717
Title of proceedings Nucleic Acids Research
DOI 10.1093/nar/gkx195

Open Access

URL https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx195
Type of Open Access Publisher (Gold Open Access)

Abstract

The nascent peptide exit tunnel has recently been identified as a functional region of ribosomes contributing to translation regulation and co-translational protein folding. Inducible expression of the erm resistance genes depends on ribosome stalling at specific codons of an upstream open reading frame in the presence of an exit tunnel-bound macrolide antibiotic. The molecular basis for this translation arrest is still not fully understood. Here, we used a nucleotide analog interference approach to unravel important functional groups on 23S rRNA residues in the ribosomal exit tunnel for ribosome stalling on the ErmC leader peptide. By replacing single nucleobase functional groups or even single atoms we were able to demonstrate the importance of A2062, A2503 and U2586 for drug-dependent ribosome stalling. Our data show that the universally conserved A2062 and A2503 are capable of forming a non-Watson–Crick base pair that is critical for sensing and transmitting the stalling signal from the exit tunnel back to the peptidyl transferase center of the ribosome. The nucleobases of A2062, A2503 as well as U2586 do not contribute significantly to the overall mechanism of protein biosynthesis, yet their elaborate role for co-translational monitoring of nascent peptide chains inside the exit tunnel can explain their evolutionary conservation.
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