Clustered codons that pair to low-abundance tRNA isoacceptors can form slow-translating regions in the mRNA and cause transient ribosomal arrest. We report that folding efficiency of the Escherichia coli multidomain protein SufI can be severely perturbed by alterations in ribosome-mediated translational attenuation. Such alterations were achieved by global acceleration of the translation rate with tRNA excess in vitro or by synonymous substitutions to codons with highly abundant tRNAs both in vitro and in vivo. Conversely, the global slow-down of the translation rate modulated by low temperature suppresses the deleterious effect of the altered translational attenuation pattern. We propose that local discontinuous translation temporally separates the translation of segments of the peptide chain and actively coordinates their co-translational folding.
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We thank M. Hayer-Hartl and U. Hartl and their groups (Max-Planck-Institute, Martinsried) for fruitful discussions, T. Palmer (University of Dundee) for providing SufI wild-type DNA and B. Berks (University of Oxford) for sharing unpublished data on the crystal structure of SufI, which was enormously helpful for our interpretations. We thank S. Arvidsson and B. Müller-Röber (University of Potsdam) for help with the RT-PCR. This work is supported by the Deutsche Forschungsgemeinschaft (Heisenberg award to Z.I. and IG73/4-1) and a Katholischer Akademischer Ausländer-Dienst fellowship to G.Z.
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Zhang, G., Hubalewska, M. & Ignatova, Z. Transient ribosomal attenuation coordinates protein synthesis and co-translational folding. Nat Struct Mol Biol 16, 274–280 (2009). https://doi.org/10.1038/nsmb.1554
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