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RiboWest2008 in Lethbridge
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Keynote speaker
Rachel Green, Johns Hopkins
Release factor-mediated quality control on the ribosome following peptide bond formation
Hani Zaher and Rachel Green
Abstract
Accurate translation of the genetic information into peptide sequences is a defining feature of the ribosome and the translation factors. While much is
known about the events that lead to ribosomal discrimination against the incorporation of the wrong amino acid, little is known about the ribosomal
response following a miscoding event. Using a well-defined in vitro bacterial translation system, we have systematically evaluated the effect of
codon:anticodon mismatches in the P and E sites on the selectivity of the A site towards release factors and aminoacylated tRNAs. Our results argue
that following a misincorporation during protein synthesis, the A site of the ribosome becomes generally promiscuous (or ram) leading ultimately to
premature release of defective polypeptide chains. The dramatic effects that we observe argue that the ribosome, like DNA polymerase, depends on a
proofreading mechanism following peptide bond formation to ensure the high fidelity of protein synthesis observed in vivo. We suggest that such a
system may play even more important roles in the cell under conditions of amino acid starvation and cellular stress and may help to explain the
stringent control of RF2 expression in bacteria.
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